XBW2015 Schedule - Ruđer Bošković Institute · XBW2015 December 14 -15, 2015 San Daniele Del Friuli hristmas Biophysics Workshops are annual scientific meetings of regional research

XBW2015 Schedule December 14-15 2015, San Daniele del Friuli Workshop day 1

9:00 to 10:00

10:00

10:10

10:30

10:50

11:10 to 11:40

11:40

12:00

12:20

12:40

13:00

Registration and Reception

WELCOME ADDRESS (G. D’Adamo and C. Micheletti)

SESSION 1: CHROMOSOME STRUCTURE AND FUNCTION (Chair M. Praprotnik )

1-A. Šiber: Conformations of circular condensed DNA bundles in bacteriophages

2-A.M. Florescu: Large-Scale chromosome fluctuations are driven by chromatin folding organization at small scales

3-L. Tubiana : Synonymous mutations of viral RNA molecules

COFFEE BREAK

SESSION II: MEMBRANES (Chair G. Pabst)

4-S. Svetina: Dependence of areal density of integral membrane proteins on membrane curvature 5-B. Geier: Asymmetric lipid vescicles at subnanometer resolution using SAXS/SANS

6-S. Šegota: AFM and force spectroscopy studies on the interaction of myricetin and myricitin with model and biological cell 7-M. Belička: Lipid domains under ionic influences 8-S. P. Gupta: Membrane interactions mediated by mono and polyvalent ions under constrained and unconstrained conditions

11:10 to 11:40

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13:30 to 15:00

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16:30-17:10

17:10

17:30

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18:10

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19:30

LUNCH SESSION III: FROM NANO TO BIO (Chair: T. Vuletič) 9-M. Lither: Solid-state nanopores: towards DNA sequencing capability 10-A. Suma: Pore translocation of polymer chains with physical knots 11-I. Delač Marion: Nanotemplates for biomolecular arrays 12-S. Marion: Stochastic model of controlled DNA translocation trough nanocapillaries

COFFEE BREAK

SESSION IV: PHYSICS OF CELLS AND TISSUES (Chair: P. Ziherl)

13-M. Krajnc: Differential tissue elasticity determines Drosophila embryo fate during gastrulation 14-D. Vurnek: Dynamics of model cell monolayers

15-J. Rozman: Buckled morphologies of confined tubular epithelium 16-V. Čadež: Formation and morphological properties of aragonite biomineral structures at nanoscale 17-A. Lucantonio: Hydraulic fracture and toughening in epithelial layers

SOCIAL DINNER

16:30 to 17:10

Workshop Day II

7:00 to 9:00 BREAKFAST

SESSION V: SOFT MATTER MODELING (Chair: G. D’Adamo) 18-P. Ziherl: Liquid-Drop model of polymer micelles 19-A. Popadić: Multiscale simulations of water flow past fullerene molecules 20-T. Škrbić: From polymers to proteins: effect of side chains and cylindrical symmetry in the formation of secondary structures within a Wang-Landau approach 21-A. Doukas: Phase diagram of spherical polymer brushes

22-M. Prapotnik: Adaptive Resolution simulations of multimolecular water models COFFEE BREAK SESSION VI: NUCLEIC ACIDS (Chair: A. Šiber)

23-Bing-Sui Lu: Molecular Recognition of dsDNA molecules by van der Waals interaction 24-K. Serec: Influence of magnesium ions on the structure of DNA investigated by FTIR spectroscopy

25-D. Grgičin: Dynamics and structure of DNA: influence of counterion valency 26-J. Zavadlav: A DNA molecule in salt solution: adaptive resolution simulation 27-M. d’Errico: Fully automated clustering by accurate non-parametric density estimation 28-S. Bottaro: RNA folding pathways in stop-motion LUNCH

9:00

9:20

9:40

10:00

10:20

10:40 to 11:10

11:10

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11:50

12:10

12:30

12:50

13:30

M. Praprotnik:

13:10 CONCLUDING REMARKS FOLLOWED BY LUNCH

XBW2015 December 14-15, 2015 San Daniele Del Friuli

hristmas Biophysics Workshops are annual scientific meetings of regional research groups from Austria, Croatia, Italy and Slovenia, in the fields of biophysics, soft matter physics, and closely related fields.

The character of the meeting is rather informal. The two-day meeting has at its core a convivial dinner. Here direct contacts, research plans and friendships can be established or maintained in a relaxed atmosphere, just before Christmas.

Organizers: Giuseppe D’Adamo & Cristian Micheletti, SISSA, Trieste-Italy.

Previous Christmas Biophysics Workshops: The workshop series were initiated in 2006 by Silvia Tomić (Zagreb) and Rudolf Podgornik (Ljubljana).

• December 15-17 2014: Buzet, Croatia; • December 16-17 2013: Dobrna, Slovenia; • December 17-18 2012: Riegersburg, Austria; • December 12-13 2011: Varaždin, Croatia; • December 10-11 2010: Ptuj, Slovenia; • December 14-15 2009: Seggau Castle, Leibnitz, Austria; • December 15-16 2008: Donja Stubica, Croatia; • December 18-19 2007: Bled, Slovenia; • December 18 2006: Zagreb, Croatia.

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14-15 December 2015San Daniele del Friuli, Italy

Conformations of circular condensed DNA bundles in bacteriophages

A. Siber1,∗

1 Institute of physics, Zagreb, Croatia* [email protected]

Some sort of DNA ”compression” is required to pack the long DNA strand in a small space, such as the cellnucleus or bacteria. Viruses have, in particular, developed several strategies to physically compress the DNAgenome molecule. In presence of basic proteins [1] or multi-valent counterions, DNA can be ”condensed”, i.e.brought to a state where it self-attracts [2]. When condensed in confinement, e.g. in virus protein coatings(capsids), it is known that the, sufficiently short, DNA also assumes toroidal conformations, but the freeenergy balance is in that case additionally complicated by the adsorption energy (DNA-capsid interaction)and by the presence of the capsid [3]. It has been proposed in the literature that the, sufficiently longDNA, may condense in conformations which are non-toroidal, i.e. which do not have the cylindrical axisof symmetry [4]. I will present a model calculation that accounts for non-toroidal conformations of DNAcondensed in confinement. The model reproduces conformations that were previously predicted [4], but alsoseveral intriguing conformations that were never predicted in the context of viruses.

References

[1] A. J. Perez-Berna, S. Marion, F. J. Chichon, J. J. Fernandez, D. C. Winkler, J. L. Carrascosa, A. C.Steven, A. Siber, and C. San Martin, Nucl. Acids Res. 43, 4274 (2015).

[2] J. Ubbink and T. Odijk, Europhys. Lett. 33, 353 (1996).

[3] A. Leforestier, A. Siber, F. Livolant, and R. Podgornik, Biophys. J. 100, 2209 (2011).

[4] N. V. Hud, Biophys. J. 69, 1355 (1995).

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Large-scale chromosome fluctuations are driven by chromatin foldingorganization at small scales

Ana Maria Florescu1,∗, Pierre Therizols2,3,4, Angelo Rosa1

1 SISSA - Scuola Internazionale Superiore di Studi Avanzati, Via Bonomea 265, 34136 Trieste(Italy)

2 INSERM UMR 944, Equipe Biologie et Dynamique des Chromosomes, Institut Universitaired’Hematologie, Hopital St. Louis, 1 Avenue Claude Vellefaux, 75010 Paris (France)

3 CNRS UMR 7212, 75010 Paris (France)4 Universite Paris Diderot, Sorbonne Paris Cite, 75010 Paris (France)

* [email protected]

Characterizing the link between small-scale chromatin structure and large-scale chromosome conformationis a prerequisite for understanding transcription. Yet, it remains poorly characterized. We present a sim-ple biophysical model, where chromosomes are described in terms of folding of a chromatin sequence withalternating blocks of 10nm and 30nm fibers. We demonstrate that chromosomes undergo prominent con-formational changes when the two fibers form separate domains. Conversely, when small stretches of 10nmfiber are randomly distributed, they act as impurities and conformational changes can be observed onlyat small length and time scales. Our results bring a limit to the possibility of detecting variations in thebehavior of chromosomes due to chromatin modifications, and suggest that the debate whether chromosomesexpand upon transcription, which is fueled by conflicting experimental observations, can be reconciled byexamining how transcribed loci are distributed. Finally, to validate our conclusions, we compare our resultsto experimental FISH data.

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Synonymous mutations of Viral RNA molecules

L. Tubiana1,2∗, A. L. Bozic2,3, C. Micheletti4, R. Podgornik2,5,6

1 Computational Physics Group, University of Vienna, Vienna, Austria2 Dept. of Theoretical Physics, Institut ”Jozef Stefan”, Ljubljana, Slovenia

3 Max Planck Institute for Biology of Ageing, Cologne, Germany4 SISSA-ISAS, Trieste,Italy

5 FMF, University of Ljubljana, Lubiana, Slovenia5 Dept. of Physics,University of Massachusetts, Amherst, Massachusetts

* [email protected]

Recent studies have shown that single-stranded viral RNAs fold into more compact structures than randomRNA sequences with similar chemical composition and identical length [1]. Based on this comparison ithas been suggested that wild-type viral RNA may have evolved to be atypically compact so as to aid itsencapsidation and assist the viral assembly process.In order to further explore the compactness selection hypothesis, we systematically compared the predictedsizes of hundreds of wild-type viral sequences with those of their mutants, which are evolved in silico and sub-ject to a number of known evolutionary constraints. In particular we considered only synonymous mutationsof coding regions and preserved the codon bias.As I will discuss in my talk, We found that the progressive accumulation of these restricted mutations stillsuffices to completely erase the characteristic compactness imprint of the viral RNA genomes, making themin this respect physically indistinguishable from randomly shuffled RNAs. This shows that maintaining thephysical compactness of the genome is indeed a primary factor among ssRNA viruses evolutionary constraints,contributing also to the low incidence of synonymous mutations in viral ssRNA genomes [2].

References

[1] A. M. Yoffe, P. Prinsen, A. Gopal, C. M. Knobler, W.M. Gelbart, A. Ben-Shaul. Proc. Natl. Acad. Sci.,105(42), 16153 (2008).

[2] L. Tubiana, A. L. Bozic, C. Micheletti and R. Podgornik, Biophys. J., 108, 194 (2015)

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Dependence of areal density of integral membrane proteins on membranecurvature

S. Svetina1,2,∗

1 Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia2 Jozef Stefan Institute, Ljubljana, Slovenia

* [email protected]

It is plausible to assume that a protein incorporated into lipid bilayer membrane causes its perturbation. Be-cause there is in general a mismatch between the intrinsic principal curvatures of such an integral membraneprotein and the bulk principal curvatures of the surrounding membrane the corresponding interaction energydepends on membrane curvature. A macroscopically defined expression for the consequent interaction termhas been derived previously[1]. Here we shall shortly reveal the reasons for its structure and describe thephysical meaning of the involved parameters[2]. The effects of this interaction term on protein areal densitywill be demonstrated by the analysis of the results of the experiment in which potassium channel KvAP wasdistributed between practically flat parts of a giant vesicle aspirated into pipette and the narrow tubulartether pulled out of it by optical tweezers[3]. The obtained dependence of the ratio between KvAP arealdensities in tubular and flat parts of the membrane on tether curvature agrees with the experimental resultin the whole range of measured tether curvatures[4]. It will be also shown how the radius of the tether atwhich this density ratio is maximal relates to the intrinsic principal curvatures of the channel. The presentedapproach to study the effects of integral membrane proteins on mechanical properties of lipid membranes willbe compared with the approach based on the assumption that these proteins act by modifying membranespontaneous curvature.

References

[1] V. Kralj-Iglic, V. Heinrich, S. Svetina, B. Zeks, Eur. Phys. J. B 10, 5-8 (1999).

[2] S. Svetina, Eur. Biophys. J. 44, 513-519 (2015).

[3] S. Aimon, A. Callan-Jones, A. Berthaud, M. Pinot, G.E.S. Toombes, P. Bassereau, Develop. Cell 28,212-218 (2014).

[4] B. Bozic, S. L. Das, S. Svetina, Soft Matter 11, 2479-2486 (2015).

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Asymmetric lipid vesicles at subnanometer resolution using SAXS/SANS

B. Geier1,2∗, D. Marquardt1,2, F.A. Heberle3, M. Doktorova4, J. Katsaras3, G. Pabst1,2

1 Institute of Molecular Biosciences, Biophysics Division, University of Graz, Austria2 BioTecMed-Graz, Graz, Austria

3 Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge; TN; USA4 Department of Physiology and Biophysics, Weill Cornell Medical College and the

Tri-Institutional Training Program in Computational Biology and Medicine, New York, NY, USA* [email protected]

Mammalian plasma membranes consist of an asymmetric lipid distribution along the bilayer, which meansthat the inner leaflet is compositional different from the outer. Bilayer asymmetry is expected to affect variousproperties of the membrane as potential, surface charge, permeability and stability. It is also hypothesizedto influence structual properties of the membrane, like area per lipid, bilayer thickness and thickness of thesingle leaflets. Due to the difficulty of preparing artificial asymmetric lipid bilayer membranes, biophysicalstudies have been mostly performed using symmetric lipid-only mimetics of plasma membranes, where innerand outer membrane leaflets have the same composition. Just recently, we developed new protocols forthe construction and characterization of asymmetric vesicles with a well-defined inner and outer leafletcomposition. Quantification of bilayer composition and degree of asymmetry enables the determination oftransverse structural parameters, such as, the area per lipid and bilayer thickness. We are able to determinethese structural parameters through a joint analysis of small angle neutron scattering (SANS) data exploitingD/H contrast variation and small angle X-ray scattering (SAXS). Here we report on the first probe-freeanalysis yielding insights into a transbilayer coupling mechanisms. First results have shown a decrease inlipid packing density at room temperature of the DPPC-rich phase (outer leaflet) compared to typical gelphase packing, indicating a disordering effect from coupling to the fluid inner leaflet.This work is supported by the Austrian Science Fund FWF, Project No.P27083-B20 (to G.P.).

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AFM and force spectroscopy studies on the interaction of myricetin andmyricitrin with model and biological cell membranes

S. Segota1,∗, V. Cadez1, M. Jazvinscak Jembrek2 and D. Vojta3

1 Division for Marine and Environmental Research, Rudjer Boskovic Institute, Zagreb, Croatia2 Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia

3 Division of Organic Chemistry and Biochemistry, Rudjer Boskovic Institute, Zagreb, Croatia* [email protected]

Interactions of flavonoids with the plasma membranes and cells exposed to the oxidative stress are notclearly understood with the respect to their influence on the membrane structure, elasticity and its func-tionality, especially regarding lipid ordering and phase behavior. Aim of this research is to study flavonoidinteractions with model lipid membranes and P19 neurons in vitro. Flavonoids exert various biological ac-tivities [1], among which anticarcinogenic [2], antiinflammatory [3] and antibacterial [4] activity. Their maincharacteristic is potent antioxidant activity, higher than that of other well-known antioxidant molecules [5].Myricetin exhibits anti-tumor and anti-inflammatory effects, strong scavenging activity [6] and more potentneuroprotective action than other compounds [7]. Myricitrin reportedly possesses effective anti-oxidative,anti-inflammatory and anti-nociceptive activities and can protect a variety of cells from stress, in vitro andin vivo [8]. Myricetin and myricitrin are flavonoids chosen to work with in order to test their ability toinhibit lipid oxidation in model membranes and in neurons in vitro, and quercetin is used as a positivecontrol.The mechanisms of interactions were investigated on two different systems. First directly on model mem-branes made of a lipid mixture with unsaturated phosphatidylcholine, sphinogomyelin and cholesterol (PC/SM/Chol ) and also on biological membranes of P19 neurons. The use of model membrane systemswas motivated by the necessity for easier deduction of the critical role that membrane lipids have in cellularuptake and to study the details of flavonoid incorporation and activity.The new aspect of this study showed that the local membrane structural reorganization is induced byperoxidation. This was achieved with combining AFM imaging data and force spectroscopy (FS). The alteredstructural and mechanical properties of neuronal membranes exposed to stress, as well as the changes withinthe cytoplasm, cell nucleus, and particularly cytoskeleton components are recorded.This study highlights the potential of AFM imaging and FS in elucidating the mechanism of flavonoidsdirectly in the plasma membrane and in the cytoplasm. The nanomechanics (elasticity), spatial organization(organization of the domains) and surface topography (roughness) of model lipid membranes and P19 neuronsas well as the structural reorganization within the cytoplasm (cell morphology, viability) that result fromthe oxidative damage are quantified by AFM for the first time.

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References

[1] D.V. Ratnam et al. J. Control. Release 113, 189 (2006).

[2] I. L. Martins et al. J. Med. Chem. 58, 4250(2015).

[3] M.M. Li et al. J. Nat. Prod., 77 2248 (2014).

[4] R. Hendra et al. Int. J. Mol. Sci. 12, 3422 (2011).

[5] N. Nuengchamnong et al. Naresuan Univ. J., 12 25 (2004).

[6] Choi Seon-Min et al. Chonnam. Med. J. 50, 45 (2014).

[7] J. G. Cho et al. J. Agric. Food. Chem. 61,10354 (2013).

[8] R. Domitrovic et al. Chem.-Biolog. Interac. 230, 21 (2015).

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Lipid domains under ionic influences

M. Belicka1,2∗, S. P. Gupta1,2, B.-S. Lu3,4, R. Podgornik3,4,5, G. Pabst1,2

1 Institute of Molecular Biosciences, Biophysics Division, NAWI Graz, University of Graz, Graz,Austria

2 BioTechMed Graz, Graz, Austria3 Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana,

Slovenia4 Department of Theoretical Physics, J. Stefan Institute, Ljubljana, Slovenia

5 Department of Physics, University of Massachusetts, Amherst, USA* [email protected]

Lipid domains are believed to play an important role as specialized platforms in lipid bilayers for a variety ofbiomacromolecules mediating a wide range of physiological functions. Their physicochemical properties areinfluenced by their composition as well as the properties of the aqueous phase. Here we focus in particular onits ionic composition. The strength and specificity of an effect brought by an individual ion onto membranesis tightly coupled to its lipid affinity, commonly known also as Hofmeister effects. In the present work we in-vestigated the effects of different monovalent anions on phase separated lipid bilayers using small-angle X-rayscattering (SAXS). The bilayers were composed a mixture of dioleoylphosphocholine (DOPC), distearoylphos-phocholine (DSPC) and cholesterol (Chol), at the ratio nDOPC : nDSPC : nChol = 0.46 : 0.3 : 0.24, known todisplay liquid-disordered (LD)/liquid-ordered (LO) phase coexistence. NaBr, NaCl or NaI salt concentra-tions were varied between c = 0 to 150 mM. The results show significant differences between the investigatedanions on LD and LO phases, with the strength following the order I− > Br− > Cl− . Thus, effects areboth ion-specific and domain-specific. We will present first insights on structural details from a full q-rangeSAXS data modelling, combining a scattering density profile model with a Caille structure factor.

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Membrane interactions mediated by mono and polyvalent ions underconstrained and unconstrained conditions

Santosh Prasad Gupta1,∗, Michal Belicka1, Bing-Sui Lu2, Heinz Amenitsch3, Rudolf Pogdornik2,Georg Pabst1

1 Institute of Molecular Biosciences, Biophysics Division, University of Graz, Graz, Austria2 Faculty of Mathematical and Physics, University of Ljubljana, Ljubljana, Slovenia

3 Institute of Inorganic Chemistry, Graz University of Technology, Austria* [email protected]

Forces are remarkably similar between colloidal particles in aqueous solution, including biological macro-molecules, proteins and membranes [1], namely electrostatic, steric, hydration, bending fluctuation, van derWaals. Here we focus on lipid membranes (bilayers), which are well established model systems for biologicalmembranes [2, 3], one of nature’s most fascinating materials, designed to separate the inner life of cells oforganelles from the outer world. These systems are of particular interest in the present context becausemembranes interact with each other via an aqueous phase. Thus properties of the aqueous phase couple toproperties of membranes and vice versa. This opens the door to manifold manipulations of membrane inter-actions e.g. by changing the ionic properties of the bathing solution. Interaction potentials (forces) betweenbiological aggregates such as lipid bilayers can be manipulated by solute ion condition (ionic strength, ionictype and valency) (unconstrained case) and by external osmotic stress (constrained case) i.e. using a large,neutral (bio) polymers such as polyethylene glycol (PEG). Using synchrotron SAXS on anionic/zwitterionicphosphatidylglycerol lipids mixed with mono and polyvalent ions, we have generated this way equal bilayerseparations for either constrained or unconstrained bilayers. Our results show that interaction potentialsdiffer significantly, in particular in terms of fluctuations around their equilibrium separations which can beunderstood in the framework of a modified Poisson-Boltzmann theory.

References

[1] R. Podgornik, D. Harries, V. A. Parsegian and H. H. Strey in Gene-Therapy-Therapeutic Mechanismsand Strategies, 2 ed., Edited by N. Smyth-Templeton (Marcel Dekker, New York (NY)), ( 2003).

[2] ] G. Pabst, N. Kucerka, M. P. Nieh, M. C. Rheinstadter and J. Katsaras Chem Phys Lipids 163, 460(2010).

[3] F. A. Heberle and G. W. Feigenson, Cold Spring Harb Perspect Biol 3, a004630 (2011).

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Solid-state nano pores: towards DNA sequencing capability

M. Lither1,∗, T. Vuletic2 and A. Radenovic1

1 Laboratory of Nanoscale Biology, LBEN - EPFL, Lausanne, Switzerland2 Institute of Physics, Zagreb, Croatia

* [email protected]

Nanopores (NP’s) have become a new single-molecule tool in biophysics. They may bring about the thirdgeneration of DNA sequencing technology that will feature long read lenghts, high throughput and minimal,labeling-free sample requirement. In comparison to biological ones, solid-state NP’s offer many advantagesdue to their robustness, high stability, tunable pore size, and a potential large scale integration into electronicdevices. The main precursor in NP preparation is a thin, solid supported membrane of e.g. Si3N4, or singleor few atomic layers twodimensional, 2D materials like MoS2 or graphene that provide the ultimate spatialresolution required for DNA sequencing. The traditional method of fabricating nanopores with nanometerprecision is based on the use of focused electron beams in transmission electron microscope (TEM) which isa time-consuming, expensive and not scalable process. Recent improvement was NP formation by controlleddielectric breakdown (DBD) of a Si3N4 membrane immersed in an electrolyte solution [1], the method whichmay be executed by the nanopore measurement setup itself. LBEN group developed an analogous methodfor controllable NP creation in single-layer MoS2 with subnanometer precision where an electrochemicalreaction (ECR) opens the pore in an atom-by-atom manner [2]. Here we emphasize that DBD and ECR asa scalable, low-cost and accessible techniques represent the enabling concepts for the design of a functionalDNA sequencing device which will require parallel integration of NPs into arrays. Meanwhile, single baserecognition still remains the challenge in NP sequencing, where controlling and reducing DNA translocationvelocity in order to facilitate the electrical read-out is an important route forward [3].

References

[1] H. Kwok, K. Briggs, V. Tabard-Cossa, PloS ONE 9(3): e92880 (2014).

[2] J. Feng, K. Liu, M. Graf, M. Lihter, R. D. Bulushev, D. Dumcenco, D. T. L. Alexander, D. Krasnozhon,T. Vuletic, A. Kis, A. Radenovic, Nano Lett. 15, 3431 (2015).

[3] J. Feng, Ke Liu, R. D. Bulushev, S. Khlybov, D. Dumcenco, A. Kis and A. Radenovic, Nature Nanotech-nology (2015) doi:10.1038/nnano.2015.219

[4] N. V. Hud, Biophys. J. 69, 1355 (1995).

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Pore translocation of polymer chains with physical knots

A. Suma1∗, A. Rosa1, C. Micheletti1

1 SISSA, International School for Advanced Studies, via Bonomea 265, I-34136 Trieste, Italy* [email protected]

The driven traslocation of knotted chains through narrow pores has important implications for single-molecule manipulation contexts. Its complex phenomenology [1] is, however, still largely unexplored, both asa function of knot complexity and the magnitude of the driving, translocating force. We accordingly reporton a systematic theoretical and computational investigation of both aspects. In particular we consider thecase of flexible chains accommodating a large repertoire of knots that are driven through pores too narrowto allow for their passage. We show that the observed rich translocation phenomenology can be rationalisedin a transparent mechanical framework that can further be used for predictive purposes [2].

References

[1] A. Rosa, M. Di Ventra and C. Micheletti. Phys. Rev. Lett, 2012, 109 , 118301

[2] A.Suma, A. Rosa and C. Micheletti. Pore translocation of knotted polymer chains, submitted, 2015

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Nanotemplates for biomolecular arrays

I. Delac Marion1∗, M. Kralj1, T. Vuletic1

1 Institut za fiziku, Bijenicka 46, 10000 Zagreb, Croatia* [email protected]

Hybrid systems consisting of a solid-state substrate functionalized or decorated with biomacromolecules arecurrently widely investigated, as they bridge the gap between living matter and technology [1]. The aim ofpresent work is to develop a method for production of an array of gold nanoclusters on a single-atomic layer,two-dimensional (2D) materials. Of interest here are 2D materials grown epitaxially on mono-crystallinesubstrates that often exhibit moire effect. This is an additional periodic corrugation of the 2D material witha period which is an order of magnitude larger than its the lattice constant. E.g. graphene grown on the(111) face of iridium monocrystal has a hexagonal moire lattice with a lattice constant of 2.5 nm, whilegraphene lattice constant is 0.24 nm [2]. Moire pattern is a very suitable template for deposition of metallicclusters. That is, metals deposited on corrugated 2D material will often form lattice of clusters which followsthe moire - thus forming a nanopattern [2]. Here, we recognize a similarity of the nanopattern length scalesand DNA diameter (or protein sizes) and also the cluster lattice as a nanotemplate for ordered attachmentof thiolated DNA chains to 2D material. We also discuss the possibility to attach a DNA origami structure,DNA tetrahedra, whose symmetry and size (5 nm) fits the nanotemplate. The novel structures could haveapplications e.g. in (bio)chemical sensing where different biomacromolecular pixels could be addressed orread directly by the underlying 2D electronic material instead by the biochemical or optical methods usedfor standard DNA chips [3, 4, 5].

References

[1] Z. Jin et al., Nat. Comm., 4, 1663 (2013)

[2] A. T. N’Diaye et al., New J. Phys., 11 , 103045 (2009)

[3] A. Sassolas et al., Chem. Rev. 108, 109 (2008)

[4] Y. Lu et al., Applied Physics Letters 97, 083107(2010)

[5] H.-Y. Park et al., ACS Nano 8, 11603 (2014)

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Stochastic model of controlled DNA translocation trough nanocapillaries

Sanjin Marion1∗, Roman D. Bulushev2, Alexandra Radenovic2

1 Institute of Physics, Bijenicka cesta 46, HR-10000 Zagreb, Croatia2 Laboratory of Nanoscale Biology, Institute of Bioengineering, School of Engineering, EPFL,

1015 Lausanne, Switzerland* [email protected]

Nanopores, nanocappilaries and similar nano-scale objects are a promising tool for future applications inDNA sequencing or single molecule experiments. Combining such an object with an external control, likeoptical tweezers, enables controlled translocation of DNA molecules trough their opening with dimensionscomparable to 10 nm. In the case of dsDNA or dsDNA with bound single proteins, one can measure theforce during controled translocation due to an external electrical field by using optical tweezers to hold themolecules in position while they are threaded through the opening[1]. Recently, it was identified that quartznanocapillaries enable a beter signal to noise ratio than typically used nanopores, and thus simultaneousmeasurements of both force and current durring translocation[2].In our recent work, DNA-protein complexes with EcoRI, RecA and RNA polymerase were studied by a simul-taneous measurement of force and current profiles during controled translocation trough quartz nanocapillaryoppenings[3]. Thus obtained force profiles were qualitatively different than previous results using nanoporesand optical tweezers. To understand the discrepancy, we used a stochastic model[1] which included theeffective motion of the DNA to explain the seen discrepancy. Different contributions to the total free energyof the protein were included, such as electrostatics, DNA entropy and bending, and electroosmotic flow. Wealso study the effects of different geometries and salt conditions to the resulting force profiles.We found that, in the case of nanocapillaries, there is a strong contribution from electroosmotic flow, due tosurface charges and geometry, which seems to change the measured charge of DNA-protein complexes[3]. Suchbehaviour implies the drag force as the dominant influence on a DNA-protein complex inside nanocapillarieswith respect to electrostatic contributions.

References

[1] A. Spiering, S. Getfert, A. Sischka, P. Reimann and D.Anselmetti, Nano Lett., 11(7), 2978 (2011).

[2] R. D. Bulushev, L. J. Steinbock, S. Khlybov, J. F. Steinbock, U. F. Keyser and A. Radenovic, NanoLett., 14(11), 6606 (2014).

[3] R. D. Bulushev, S. Marion and A. Radenovic, Nano Lett., 15(10), 7118 (2015).

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Differential tissue elasticity determines Drosophila embryo fate duringgastrulation

M. Rauzi1, U. Krzic1, T. E. Saunders1, M. Krajnc2∗, P. Ziherl2,3,4, L. Hufnagel1, M. Leptin1

1 European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg,Germany

2 Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia3 Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana,

Slovenia4 Erwin Schrodinger International Institute for Mathematical Physics, University of Vienna,

Boltzmanngasse 9, A-1090, Vienna, Austria* [email protected]

We study the mechanics of embryonic epithelium in Drosophila during gastrulation. In this early-stagedevelopmental process, a furrow is formed on the ventral side of the embryo. Recent experiments reveal acollective pattern of cell displacement and deformation involving the whole embryo, and they show that thedifferent cell populations in the tissue are mechanically distinct and thus respond differently to the apicalconstriction and invagination of the mesoderm [1]. In particular, the dorsal tissue is stretched by about50% and the lateral tissue moves ventrally without deforming significantly. To study the mechanics of theepithelium during gastrulation, we use a 2D theoretical model of droplet-like cells, characterized by corticaltension, apico-basal differential tension, and cell-cell adhesion [2, 3]. Within this model, apical constrictionin ventral cells is driven by an increased apico-basal differential tension which triggers furrow formation. Thedifferential elastic response of the lateral and the dorsal tissue is governed by their effective Young moduliwhich depend on differential cortical tension of the two cell populations [3]. The experimental observationsof the developing embryo are best captured by imposing a very small cortical tension in the dorsal cells anda large cortical tension in the lateral cells compared to the ventral cells [1]. These theoretical predictionsare conrmed by ablation experiments in actomyosin cortical meshwork, showing that a complex collectivemechanics of the gastrulating embryo might be driven by a relatively simple physical process [1].

References

[1] M. Rauzi, U. Krzic, T. E. Saunders, M. Krajnc, P. Ziherl, L. Hufnagel, and M. Leptin, Nat. Commun.,6:8677 (2015).

[2] A. Hocevar Brezavscek, M. Rauzi, M. Leptin, and P. Ziherl, Biophys. J., 103, 1069 (2012).

[3] M. Krajnc, N. Storgel, A. Hocevar Brezavscek, and P. Ziherl, Soft Matter, 9, 8368 (2013).

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Dynamics of model cell monolayers

D. Vurnek1∗, S. Kaliman1, C. Wollnik2, P. Linke2, F. Rehfeldt2, D. Dudziak3, A-S. Smith1,4

1 Institute for Theoretical Physics, Cluster of Excellence: EAM, University ofErlangen-Nuremberg

2 Third institute of Physics-Biophysics, Georg-August University, Gottingen3 Universitatsklinikum Erlangen, University of Erlangen-Nuremberg4 Division of Physical Chemistry, Institute Rudjer Boskovic, Zagreb

* [email protected]

Morphogenesis and wound healing both require migration of large number of constituent cells. We addressthis question by using MDCK II model epithelium grown on, collagen I coated, glass substrates. Usually,to study such a system, a part of an expanding monolayer is carefully analyzed. Here, we take the comple-mentary approach and look at the global development of an, initially droplet seeded, system of cells whichis allowed to expand freely over time. In contrast to most studies, majority of our experiments preformedhave time windows of at least 10 days. On the basis of experimental findings the (known) model of expo-nential growth of small (< 0.1mm2) cell clusters is expanded with one additional parameter which accountsfor the slowing down of area growth. Thus, with the use of a simple differential equation, with three in-tuitive parameters one can successfully describe the area expansion of clusters in the range of 4 orders ofmagnitude. Further data analysis shows a stunning picture of a perpetually accelerating monolayer edge, instark opposition with the concept of constant speed limits supposedly reached by macroscopic (> 10mm2)monolayers.

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Buckled morphologies of confined tubular epithelium

J. Rozman1,∗, M. Krajnc2, P. Ziherl1,2

1 Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana,Slovenia

2 Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia* [email protected]

We theoretically study the shape of single-layer thick epithelial tissues confined to a rigid tube. Within the2D implementation of the tension-based mechanical model [1, 2], we compute the cross-section of the tissuebuckled due to apico-basal differential tension. The cross-section is characterized by the number of lobeswhich generally increases with the differential tension. We find that for small enough tube radius, transitionfrom the few-lobes regime to the many-lobes regime is discontinuous so that the morphological phase diagramfeatures a critical point terminating the transition. The results are compared to the predictions of othermodels as well as to experimentally observed tubular epithelia in, e.g., the developing chick gut.

References

[1] A. Hocevar Brezavscek, M. Rauzi, M. Leptin, P. Ziherl, Biophys. J., 103, 1069 (2012)

[2] M. Krajnc, N. Storgel, A. Hocevar Brezavscek, P. Ziherl, Soft Matter, 9, 8368 (2013)

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Formation and morphological properties of aragonite biomineral structures atthe nanoscale

V. Cadez1, S. D. Skapin2, B. Salopek Sondi1, S. Segota1 and I. Sondi3,∗

1 Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia2 J. Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia

3 Faculty of Mining, Geology and Petroleum Engineering, University of Zagreb, Pierottijeva6,10000 Zagreb, Croatia

* [email protected]

This study describes complex structural and morphological properties of hierarchically organized biomineralaragonite structures of the pillow coral (Cladocora caespitosa), Noah’s ark (Arca noae), noble fan mussel(Pinna nobilis) and common cuttlefish (Sepia officinalis) and review the tangled mechanism of their for-mation at the nanoscale. The structures and morphologies of aragonite biominerals were examined usingX-ray diffraction (XRD) and field-emission scanning electron microscopy (FESEM), their thermal propertiesby thermogravimetric analyses (TGA) and differential thermal analysis (DTA). Soluble proteins from theorganic matrix were investigated using gel electrophoresis (SDS-PAGE and 2-DE PAGE).The results obtained show that examined species form hierarchically organized biomineral structures throughthe oriented aggregation processes of the nanosized aragonite crystallites. Aggregated forms are still visiblein the entirely designed biominerals, exhibiting well-defined and uniform nanosized building blocks associatedwith the organic components. These processes produce morphologically diverse aragonite structures in eachspecies that is primarily governed by the character of the organic components, mainly soluble proteins.As a final remark, this study demonstrates how these aragonite producing organisms may take an advantageof a variety of proteins to manipulate the formation and morphology of biogenic aragonite at the nanoscale.Understanding these mechanisms may lead to new strategies for the synthesis of biomaterials with desirableproperties and to improve insight into their role in the hard tissues formation of many mineralizing organisms[1, 2, 3].

This work has been supported in part by Croatian Science Foundation under the project 2504.

References

[1] I. Sondi, B. Salopek-Sondi, S. D. Skapin, S. Segota, I. Jurina and B. Vukelic, J. Colloid Interface Sci.354, 181 (2011).

[2] I. Sondi, S.D. Skapin, I. Jurina and D. Slovenec. Geologia Croatica 64/1, 61 (2011).

[3] I. Sondi and S. D. Skapin in ”Biomimetics, Learning from Nature”, ed. Amitava Mukherjee (InTech,Viena), p 241 (2010).

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Hydraulic fracture and toughening in epithelial layers

A. Lucantonio1, G. Noselli1, X. Trepat2, A. DeSimone1,∗, M. Arroyo3,†

1 SISSA - International School for Advanced Studies, via Bonomea 265, 34136 Trieste, Italy2 IBEC - Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, 08028 Barcelona, Spain

3 UPC - Universitat Politecnica de Catalunya, Carrer Jordi Girona 1, 08034 Barcelona, Spain* [email protected]

† [email protected]

Epithelial cell layers are soft biological tissues capable of performing a variety of functions (e.g., morphogen-esis, wound healing, protection against environmental pathogens) while routinely operating in the presenceof significant levels of stretch, such as those arising from breathing manoeuvres, cardiac pulses or peristalticcontractions. These mechanical stimuli may cause epithelial fracture, possibly leading to severe clinical con-ditions. Epithelial fracture is commonly associated with the excessive stress that arises at cell-cell junctionsunder tensile loading. Quite surprisingly, recent in vitro experiments [1] on cell clusters adhered to a hydrogelsubstrate and subject to stretch-unstretch cycles have shown that failure of the monolayer can actually takeplace under compressive loading. Moreover, in the experiments, fracture was typically accompanied by thesimultaneous growth of multiple, intercellular cracks.To rationalize these experimental observations, we study the ideal case of a brittle elastic layer containingedge cracks and bonded to a hydrogel substrate. Remarkably, we show that the brittle material can fracturein compression and can resist cracking in tension, thanks to the hydraulic coupling with the hydrogel. In thecase of multiple cracks, we find that localized fracture occurs [2] when the permeability of the hydrogel ishigh, whereas decreased permeability leads to toughening by promoting multiple cracking. We believe thatour results [3] may contribute to the understanding of fracture in biological tissues and provide inspirationfor the design of tough, biomimetic materials.

References

[1] L. Casares, R. Vincent, D. Zalvidea, N. Campillo, D. Navajas, M. Arroyo, X. Trepat, Nat. Mater., 14,343-351 (2015).

[2] G. Noselli, V. S. Deshpande, N. A. Fleck, Int. J. Fracture, 183, 241-258 (2013).

[3] A. Lucantonio, G. Noselli, X. Trepat, A. DeSimone, M. Arroyo, Phys. Rev. Lett., 115, 188105 (2015).

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Liquid-drop model of polymer micelles

P. Ziherl1,2,∗, C. N. Likos3

1 Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana,Slovenia

2 Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia3 Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Vienna, Austria

* [email protected]

We introduce a coarse-grained model to theoretically describe the deformation of a spherical polymer brush(SPB) in confinement. Here the SPB is represented by a liquid drop with an effective free energy containinga phenomenological bulk term and a surface term. The equilibrium shape and thus the elastic deformation ofthe drop are controlled by the ratio the Egelstaff-Widom length [1], which is a material parameter combiningcompressibility and surface tension, and the diameter of the SPB. We present scaling arguments to showthat in SPBs, the value of the reduced Egelstaff-Widom length is universal, i.e., independent of the numberof chains in the brush and on their length [2]. This suggests that the deformation behavior of the SPBsshould be rather generic, which is consistent with experimental studies of the structure of dense suspensionsof dendrimers and block-copolymer micelles.

References

[1] P. A. Egelstaff, B. Widom, J. Chem. Phys., 53, 2667 (1970)

[2] J. Riest, L. Athanasopoulou, S. A. Egorov, C. N. Likos, P. Ziherl, Sci. Rep., 5, 15854 (2015)

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Multiscale simulations of water flow past fullerene molecules

A. Popadic1∗, M. Praprotnik1,2

1 Laboratory for Molecular Modeling, National Institute of Chemistry, Hajdrihova 19, SI-1001Ljubljana, Slovenia

2 Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska19, SI-1000 Ljubljana, Slovenia* [email protected]

We propose the use of the Navier-Stokes equations subject to partial-slip boundary conditions to simulatewater flows past fullerene molecules. The finite volume discretizations of the Navier-Stokes equations arecombined with slip lengths extracted from molecular dynamics (MD) simulations to describe fluid flows atthe nanoscale. The flow quantities calculated from the present hybrid approach are in excellent agreementwith pure MD results while they are obtained at a fraction of the computational cost. Our method enablessimulations of system sizes and times well beyond the present capabilities of MD simulations.

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From polymers to proteins: effect of side chains and cylindrical symmetry inthe formation of secondary structures within a Wang-Landau approach

T. Skrbic1∗, A. Badasyan2, T. X. Hoang3, R. Podgornik1,3∗, A. Giacometti1

1 Dipartimento di Scienze Molecolari e Nanosistemi, Universita Ca’ Foscari di Venezia, CampusScientifico, Edificio Alfa, via Torino 155,30170 Venezia Mestre, Italy

2 Material Research Laboratory, University of Nova Gorica, SI-5270 Ajdovscina, Slovenia3 Center for Computational Physics, Institute of Physics, VAST 10 Dao Tan St., Hanoi, Vietnam

4 Department of Theoretical Physics, J. Stefan Institute and Department of Physics, Faculty ofMathematics and Physics, University of Ljubljana - SI-1000 Ljubljana, Slovenia

* [email protected]

We study the equilibrium properties of a flexible homopolymer whose consecutive monomers are representedby impenetrable hard spherical beads, tangent to each other and non-consecutive monomers that interact viaa square-well potential. To this aim, we use both replica exchange canonical simulations and micro-canonicalWang-Landau techniques and performing a close comparative analysis of the corresponding results, findingperfect agreement with each other and results previously reported in literature. The model is then refined intwo different directions. By allowing partial overlapping between consecutive beads, we break the sphericalsymmetry, thus providing a sever constraint on the possible chian conformations. This leads to a groundstate that is either helical, planar or globular, depending on the range of the interactions. Alternatively, weintroduce additional spherical beads at specific positions to represent the steric hindrance of the side chainsin real proteins. While for short chains, the ground state is found to be a globule, the helical ground stateemerges for longer chains (few tens of beads). The combination of the two above effects is found to increasethe stability of the secondary structures, in agreement with past results. The fundamental role played bythe range of the square-well attraction is enlighted and it is shown to play a role similar to that found insimple liquids and polymers. Perspectives in terms of protein folding are finally discussed.

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Phase diagram of spherical polymer brushes

A. K. Doukas1, C. N. Likos2, and P. Ziherl1,3

1 Jozef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia2 Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Wien, Austria

3 Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Slovenia

We theoretically study the phase diagram of dense solutions of spherical polymer brushes as prototypenanocolloidal particles. Within a coarse-grained continuum model where the brush is represented by a liquiddroplet, its free energy consists of a phenomenological bulk term and of a surface term. We focus on largedensities where the brushes are expected to form crystalline phases, and we numerically compute the freeenergy of the drop in various lattices including face-centered cubic (FCC), hexagonal close-packed (HCP),body-centered cubic (BCC), simple cubic (SC), body-centered tetragonal (BCT), simple hexagonal (SH), andA15 lattice. We construct the phase diagram to find that it only contains the FCC and the A15 lattice atsmall and large densities, respectively. We also study a generalized version of the model where the tensionsof the free and the contact surface of the drop are different. Our results elucidate several experimentalobservations reported in solutions of diblock copolymer micelles, star polymers, and dendrimers.

References

[1] Riest J. et al. Elasticity of polymeric nanocolloidal particles. Sci. Rep. 5, 15854; doi: 10.1038/ srep15854(2015)

[2] Ziherl P., Kamien R.D., Maximizing entropy by minimizing area: towards a new principle of self-organization. J. Phys. Chem. B, 2001, 105 (42), pp 10147?10158; doi: 10.1021/jp010944q (2001)

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Adaptive resolution simulations of multimolecular water models

J. Zavadlav1, M. Praprotnik1,2∗


2 Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska19, SI-1000 Ljubljana, Slovenia

* [email protected]

We present adaptive resolution molecular dynamics simulations of aqueous solvents using coarse-grainedmolecular models that are compatible with the MARTINI force field [1]. The solvent molecules change theirresolution back and forth between the atomistic and coarse-grained representations according to their posi-tions in the system. The difficulties that arise from coupling to a coarse-grained model with a multimoleculemapping could be successfully circumvented by using bundled water models. We discuss the advantages andlimitations of this multiscale approach on several examples, e.g., coupling of atomistic water with polarizable[2] and non-polarizable [3] coarse-grained water models.

References

[1] J. Zavadlav, M. N. Melo, S. J. Marrink, M. Praprotnik, J. Chem. Phys. 140, 054114 (2014)

[2] J. Zavadlav, M. N. Melo, S. J. Marrink, M. Praprotnik, J. Chem. Phys. 142, 244118 (2015)

[3] J. Zavadlav, M. N. Melo, A. V. Cunha, A. H. de Vries, S. J. Marrink, M. Praprotnik, J. Chem. TheoryComput. 10 2591 (2014)

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Molecular recognition of dsDNA molecules by van der Waals interaction

Bing-Sui Lu1∗, Ali Naji2, Rudolf Podgornik1

1 Institut “Jozef Stefan”, Jamova cesta 39, 1000 Ljubljana, Slovenija2 School of Physics, Institute for Research in Fundamental Sciences (IPM), P.O. Box

19395-5531, Tehran, Iran* [email protected]

Van der Waals forces are highly prevalent in Nature, underlying many everyday processes that we take forgranted (for example, the sticking of geckos to walls). In this talk, we look at how van der Waals forcescan result in a stronger attraction between short double-stranded (ds) DNA molecules in salt solution, if thechemical sequences of the two molecules are identical and more heterogeneous, and the two molecules areoriented in parallel. [1, 2]

References

[1] B.-S. Lu, A. Naji and R. Podgornik, “Molecular recognition by van der Waals interaction betweenpolymers with sequence-specific polarizabilities.” J. Chem. Phys. 142, 214904 (2015).

[2] B.-S. Lu, A. Naji and R. Podgornik, “Van der Waals interaction between polymers with sequence-specificpolarizabilities: Stiff polymers and flexible Gaussian coils.” arXiv:1509.01996

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Influence of magnesium ions on the structure of DNA investigated by FTIRspectroscopy

K. Serec1, S. Dolanski Babic1,2, S. Tomic2

1 School of Medicine, University of Zagreb, Croatia2 Institut za fiziku, Zagreb, Croatia

* [email protected]

Previous research showed that under influence of Mg+2 cations DNA undergoes structural and conformationalchanges [1, 2, 3, 4, 5, 6]. It was pointed out by many authors that regardless of the conditions, Mg ions showgreat affinity toward phosphate groups of DNA, thus neutralizing and stabilizing double helical structure.Interaction of the Mg ions with the base sites, however, still remains unclear as different authors reportdifferent affinities and preferable sites of Mg-base coordination [1, 2, 5, 6]. Thus, possibility and particularmechanism of Mg-DNA interaction still remains unclear, as experimental data is often not consistent. Inorder of finding the best model, we developed protocols where Mg-DNA interaction can be tested with andwithout intrinsic Na cations, and over large interval of molar concentrations ratio (r=[Mg2+]/[P]).Fourier Transform Infrared spectroscopy was used to determine the effects of Mg+2 ions on the structureand conformation of DNA in thin films. Since DNA is highly sensitive to quantity of metal ions, sampleswere prepared in such a way as to have r over 4 orders of magnitude (r= 0.0067 to 30). Also, in orderto eliminate/determine influence of sodium ions extensive dialysis was performed, and then compared withsamples containing sodium ions.

References

[1] Bhattacharyya, R.G., K.K. Nayak, and A.N. Chakrabarty, Inorganica Chimica Acta-Bioinorganic Chem-istry, 1988. 153(2): p. 79-86.

[2] Langlais, M., H.A. Tajmirriahi, and R. Savoie, Biopolymers, 1990. 30(7-8): p. 743-752.

[3] Duguid, J., et al., Biophysical Journal, 1993. 65(5): p. 1916-1928.

[4] Duguid, J.G., et al., Biophysical Journal, 1995. 69(6): p. 2623-2641.

[5] Hackl, E.V., S.V. Kornilova, and Y.P. Blagoi, International Journal of Biological Macromolecules, 2005.35(3-4): p. 175-191.

[6] Ahmad, R., H. Arakawa, and H.A. Tajmir-Riahi, Biophysical Journal, 2003. 84(4): p. 2460-2466.

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Dynamics and structure of DNA: influence of counterion valency

D. Grgicin1, T. Vuletic1

1 Institut za fiziku, Bijenicka cesta 46, Zagreb

DNA solution structure is studied with dielectric spectroscopy (DS) at least since 1976[1]. Despite such along run the researchers still do not agree about the nature of counterion relaxation in MHz range and theorigin of the observed length scale L - whether the relaxation is perpendicular or parallel to the polyion andwhther the free or Manning condensed counterions are the relaxing entities [2, 3, 4, 5, 6, 7, 8, 9]. Basicallywhat was know was only that for semidilute solution L ∝ c−0.5 and for dilute L ∝ c−0.33.As a control, for semidilute solutions of biopolelectrolytes we measured de Gennes correlation length (polymermesh size) ξ by small angle X-ray scattering (SAXS) and found that it expectedly scales as L ∝ c−0.5 butis 5-6 times larger [10]. We tested also the scenario of denaturation of DNA. Here we observe a decreasein characteristic length scale L obtained with DS - this goes well with an expected decrease in ξ due tothe simple fact that the number of chains in solution doubles. Consistent picture to be built from thesefindings is that the free counterions relax perpendicular to the polyion and the characteristic diameter of therelaxation volume L is the distance from the polyion at which the potential felt by the counterions falls tokT, as shown in the figure. In parallel, in order to be able to deal with the free counterion concentrationsand estimate the counterion extent around the polyion we measured the Manning condensation coefficientvia conductometry and also the osmotic coefficient related to the Manning coefficient we obtained by SAXS[11, 12].

relaxation

30

References

[1] M. Sakamoto, H. Kanada, R. Hayakawa, Y. Wada, Biopolymers, 15, 879 (1976)

[2] B. Saif, R. K. Mohr, C. J. Montrose, T. A. litovitz, Biopolymers, 31, 1171 (1991)

[3] R. S. Lee, S. Bone, Biochimica et Biophysics Acta,1397, 316, (1998)

[4] C. Gabriel, E. Grant, Bioelectromagnetics, 20, 40, (1999)

[5] D. J. Bakewell, I. Ermolina, H. Morgan, J. Milner, Y. Feldman, Biochimica et Biophysica Acta, 1493,151, (2000)

[6] S. Omori, Y. Katsumoto, A. Yasuda, K. Asami, Physical Review E, 73,0509011, (2006)

[7] Y. Katsumoto, S. Omori, D. Yamamoto, A. Yasudu, Physical Review E, 75, 011911, (2007)

[8] D. Grgicin, S. Dolanski Babic, T. Ivek, S. Tomic, Phys. Rev. E 88, 052703 (2013)

[9] E. Ermilova, F. F. Bier, R. Holzel, Phys. Chem. Chem. Phys., 16, 11256,(2014)

[10] K. Salamon, D. Aumiler, G. Pabst, T. Vuletic, Macromolecules, 46, 1107 (2013)

[11] T. Vuletic, S. Dolanski Babic, D. Grgicin, D. Aumiler, J. Radler, F. Livolant, S. Tomic, Phys. Rev. E,83, 041803, (2011)

[12] Ida Delac Marion, D. Grgicin, K. Salamon, S. Bernstorff, T. Vuletic, Macromolecules, 48, 2286, (2015)

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A DNA Molecule in salt solution: Adaptive Resolution simulation

J. Zavadlav1∗, R. Podgornik2,3, M. Praprotnik1,2


2 Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska19, SI-1000 Ljubljana, Slovenia

3 Theoretical Physics Department, J. Stefan Institute, Jamova c. 39, SI-1000 Ljubljana, Slovenia* [email protected]

We present an adaptive resolution simulation (AdResS) [1, 2] of a DNA molecule in multiscale salt (1MNaCl) solution at ambient conditions. The DNA is always modeled at full atomistic resolution using theAMBER 03 force field. The solvent’s level of representation changes adaptively according to distance fromthe DNA’s center of mass from atomistic (at short distances) to coarse-grained (at larger distances) and viceversa. We observe within our error bars no differences in structural (e.g., root mean squared deviation andfluctuations of backbone heavy atoms, dielectric constant, and the average occupancy and residence time ofsodium and oxygen atoms of water around the electronegative atoms of DNA) and dynamical properties ofthe DNA between the adaptive resolution and fully atomistically solvated models.

References

[1] M. Praprotnik, L. Delle Site, K. Kremer, Annu. Rev. Phys. Chem., 59, 545 (2008)

[2] J. Zavadlav, R. Podgornik, M. Praprotnik, J. Chem. Theory Comput., 11, 5035 (2015)

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Fully automated clustering by accurate non-parametric density estimation

M. d’Errico1∗, A. Laio1, E. Facco1, A. Rodriguez1

1 SISSA (Trieste)* [email protected]

The use of the right density estimates in the framework of density-based cluster analysis is one of the keys toreveal the properties of a given dataset. We developed a new unsupervised and adaptive density estimator[1], that is able to reconstruct the point local density in an accurate way, even in highly inhomogeneousdatasets. By combining the new density estimator with a generalized version of a recently developed cluster-ing approach [2], we can automatically recognize sets of data points organized in clusters, regardless of thedataset characteristics (i.e. space dimensionality, shape of the clusters, distance metrics). We demonstratethe power of the algorithm performing cluster analyses on biological systems to disentangle complexity pat-terns. In particular, interesting results have been obtained by analyzing rRNA sequences from human GUTmicrobiota.

References

[1] M. d’Errico, A. Laio, E. Facco and A. Rodriguez, “An accurate and unsupervised density estimator forhighly inhomogeneous datasets” (In preparation).

[2] A. Rodriguez, A. Laio, “Clustering by fast search and find density peaks”, Science, 2014, 344, 1492-1496

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RNA folding pathways in stop-motion

Sandro Bottaro∗,1, Alejandro Gil-Ley1, and Giovanni Bussi1

1 SISSA Via Bonomea 265, 34136 Trieste, ITALY* [email protected], [email protected]

We introduce a new, efficient method for studying and predicting folding pathways of RNA molecules. Themethod is based on the idea that three-dimensional fragments extracted from available crystal structuresprovide information for constructing conformational ensembles of short RNA molecules. We show theseensembles of fragments to be in quantitative agreement with available NMR spectroscopy data. In contrast,equilibrium ensembles obtained from extensive, atomistic molecular dynamics simulations present noticeableartifacts not compatible with experimental data.The idea of using fragments ensemble for biomolecular modeling is not new, but it has been mainly employedfor structure-prediction problems. Here, we extend the scope of fragments ensembles, as we use them not onlyto describe the stable states, but also intermediates connecting them, thereby constructing reaction pathways.I will present a unified theoretical framework for obtaining such pathways, building upon our recent studyon RNA structure[1], as well as on established concepts from Markov state models[2] and diffusion maps[3].The method is employed to study the folding pathways of the most important RNA tetraloops (GNRA andUNCG). A proper in-silico characterization of these systems using all-atom molecular dynamics simulationsis still hindered by its extremely high computational cost as well as by the known inaccuracies of state-of-the-art force fields. We present an atomic-detailed mechanistic description of the helix-to-loop folding ofGNRA and UNGC tetraloops, discussing the results in the lights of previous experimental and computationalstudies.

References

[1] Bottaro S, Di Palma F, Bussi G, Nucleic Acids Res 42, 13306 (2014)

[2] Noe F, Schuette C, Vanden-Eijnden E, Reich L, Weikl TR, Proc Natl Acad Sci U S A 106, 19011 (2009)

[3] Coifman RR et al. , Proc Natl Acad Sci U S A 102, 7426 (2005)

34

List of Participants Austria

Ø Michal Belicka, Institute of Molecular Biosciences, Graz Ø Barbara Geier, Institute of Molecular Biosciences, Graz Ø Santosh Prasad Gupta, Institute of Molecular Biosciences, Graz Ø George Pabst, Institute of Molecular Biosciences, Graz Ø Michal Pachler, Institute of Molecular Biosciences, Graz Ø Luca Tubiana, Universität Wien, Wien.

Croatia

Ø Vida Čadež, Ruder Bošković Institute, Zagreb Ø S. Dolanski Babić, Medicinski fakultet, Zagreb Ø Danijel Grgičin, Institute of physics, Zagreb Ø Ida Delač Marion, Institute of physics, Zagreb Ø Sanjin Marion, Institute of physics, Zagreb Ø Suzana Šegota, Ruder Bošković Institute, Zagreb Ø Kristina Serec, Medicinski fakultet, Zagreb Ø Antonio Šiber, Institute of physics, Zagreb Ø Tomislav Vuletić, Institute of physics, Zagreb.

Germany

Ø Damir Vurnek, Institute for Theoretical Physics, Nuremberg. Italy

Ø Sandro Bottaro, SISSA, Trieste Ø Giuseppe D’Adamo, SISSA, Trieste Ø Maria d’Errico, SISSA, Trieste Ø Ana Maria Florescu, SISSA, Trieste Ø Alessandro Lucantonio, SISSA, Trieste Ø Cristian Micheletti, SISSA, Trieste Ø Tatjana Skrbic, Università ca’ Foscari, Venezia Ø Antonio Suma, SISSA, Trieste.

35

Slovenia

Ø Andreas Doukas, Jožef Stefan Institute, Ljubliana Ø Mateji Krainc, Jožef Stefan Institute, Ljubljana Ø Bing-Sui Lu, Jožef Stefan Institute, Ljubljana Ø Aleksandar Popadić, Laboratory for Molecular Modeling, Ljubljana Ø Matej Praprotnik, Laboratory for Molecular Modeling, Ljubljana Ø Jan Rozman, Jožef Stefan Institute, Ljubljana Ø Sasa Svetina, Institute of Biophysics, Ljubliana Ø Julija Zavadlav, Laboratory for Molecular Modeling, Ljubljana Ø Primoz Ziherl, Jožef Stefan Institute, Ljubljana.

Swiss Confederation

Ø Marthina Lither, École polytechnique fédérale de Lausanne, Lausanne.

36

Contents

1 Workshop Schedule 1

2 Introduction 4

3 A. Siber: Conformations of circular condensed DNA bundlesin bacteriophages 5

4 A.M. Florescu: Large-scale chromosome fluctuations are drivenby chromatin folding organization at small scales 6

5 L. Tubiana: Synonymous mutations of Viral RNA molecules 7

6 S. Svetina: Dependence of areal density of integral membraneproteins on membrane curvature 8

7 B. Geier: Asymmetric lipid vesicles at subnanometer resolutionusing SAXS/SANS 9

8 S. Segota: AFM and force spectroscopy studies on the interac-tion of myricetin and myricitrin with model and biological cellmembranes 10

9 M. Belicka: Lipid domains under ionic influences 12

10 S. Gupta: Membrane interactions mediated by mono and poly-valent ions under constrained and unconstrained conditions 13

11 M. Lither: Solid-state nano pores: towards DNA sequencingcapability 14

12 A. Suma: Pore translocation of polymer chains with physicalknots 15

13 I. Delac Marion: Nanotemplates for biomolecular arrays 16

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14 S. Marion: Stochastic model of controlled DNA translocationtrough nanocapillaries 17

15 M. Krajnc: Differential tissue elasticity determines Drosophilaembryo fate during gastrulation 18

16 D. Vurnek: Dynamics of model cell monolayers 19

17 J. Rozman: Buckled morphologies of confined tubular epithe-lium 20

18 V. Cadez: Formation and morphological properties of aragonitebiomineral structures at the nanoscale 21

19 A. Lucantonio: Hydraulic fracture and toughening in epitheliallayers 22

20 P. Ziherl: Liquid-drop model of polymer micelles 23

21 A. Popadic: Multiscale simulations of water flow past fullerenemolecules 24

22 T. Skrbic: From polymers to proteins: effect of side chains andcylindrical symmetry in the formation of secondary structureswithin a Wang-Landau approach 25

23 A. Doukas: Phase diagram of spherical polymer brushes 26

24 M. Praprotnik: Adaptive resolution simulations of multimolec-ular water models 27

25 B.-S. Lu: Molecular recognition of dsDNA molecules by vander Waals interaction 28

26 K. Serec: Influence of magnesium ions on the structure of DNAinvestigated by FTIR spectroscopy 29

27 D. Grgicin: Dynamics and structure of DNA: influence of coun-terion valency 30

28 J. Zavadlav: A DNA Molecule in salt solution: Adaptive Res-olution simulation 32

29 M. d’Errico: Fully automated clustering by accurate non-parametricdensity estimation 33

30 S. Bottaro: RNA folding pathways in stop-motion 34

31 S. Bottaro: List of Participants 35

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XBW2015 Schedule - Ruđer Bošković Institute · XBW2015 December 14 -15, 2015 San Daniele Del Friuli hristmas Biophysics Workshops are annual scientific meetings of regional research