DOI: 10.1126/science.1235357, 1281 (2013);339 Science

Ingo SethmannCreating Flexible Calcite Fibers with Proteins

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www.sciencemag.org SCIENCE VOL 339 15 MARCH 2013 1281

PERSPECTIVES

be equipped to monitor processes affecting

global mercury transport and cycling. The

United Nations Environment Programme

recently identif ied two pressing global

issues with regard to mercury pollution:

establishing the link among deposition,

methylation, and uptake by living organ-

isms, and characterizing methylation and

demethylation and how these reactions are

affected by climate change ( 14).

The study by Parks et al. is important

and timely for its promise to inform the

development of such monitoring and man-

agement strategies. Knowing the sequences

of mercury methylation genes will be use-

ful for the development of molecular bio-

markers for the detection and quantifi cation

of mercury methylation and the elucidation

of the environmental triggers of hgcA/hgcB

expression. Given that quantitative and tra-

ditional polymerase chain reactions can

now be performed in the fi eld, these bio-

markers would offer specific, fast analy-

ses of whether or not methylation is likely

to occur in a given environment, as well as

enable evaluation of the effi ciency of poten-

tial mitigation strategies. Further work may

reveal additional determinants of mercury

methylation under anoxic conditions and

might explain puzzling observations of

methylation under oxic conditions in sur-

face marine waters ( 15).

References

1. H. Hintelmann, K. Keppel-Jones, R. D. Evans, Environ.

Toxicol. Chem. 19, 2204 (2000).

2. B. A. Bergquist, J. D. Blum, Science 318, 417 (2007).

3. J. M. Parks et al., Science 339, 1332 (2013);

10.1126/science.1230667.

4. S. Jensen, A. Jernelöv, Nature 223, 753 (1969).

5. G. Compeau, R. Bartha, Appl. Environ. Microbiol. 50, 498

(1985).

6. E. J. Kerin et al., Appl. Environ. Microbiol. 72, 7919 (2006).

7. S.-C. Choi, T. Chase Jr., R. Bartha, Appl. Environ. Microbiol.

60, 4072 (1994).

8. J. M. Wood, F. S. Kennedy, C. G. Rosen, Nature 220, 173

(1968).

9. S. Hamelin, M. Amyot, T. Barkay, Y. Wang, D. Planas, Envi-

ron. Sci. Technol. 45, 7693 (2011).

10. C. C. Gilmour et al., Appl. Environ. Microbiol. 77, 3938

(2011).

11. L. Landner, Nature 230, 452 (1971).

12. J. K. Schaefer et al., Proc. Natl. Acad. Sci. U.S.A. 108, 8714

(2011).

13. L. Boto, I. Doadrio, R. Diogo, Biol. Philos. 24, 119 (2009).

14. U.N. Environment Programme DTI/1636/GE (2013).

15. I. Lehnherr, V. L. St. Louis, H. Hintelmann, J. L. Kirk, Nat.

Geosci. 4, 298 (2011).

Creating Flexible Calcite Fibers with Proteins

MATERIALS SCIENCE

Ingo Sethmann

Fracture-resistant calcium carbonate fi bers

were made by using a protein that normally

directs silica spicule formation in sponges.

The process of biomineralization that

forms structures such as bones, teeth,

and shells of organisms incorporates

biomacromolecules (proteins) into miner-

als as they precipitate. The composite nature

of these materials confers flexibility and

elasticity on otherwise brittle minerals, so

biominerals can exhibit high performance

rarely reproduced by synthetic or biomi-

metic materials. On page 1298 of this issue,

Natalio et al. ( 1) describe the synthesis of

intriguingly fl exible fi brous spicules of cal-

cite (CaCO3) using silicatein-α, a protein

involved in the formation of skeletal silica

(hydrated SiO2) spicules in sponges, to facil-

itate biomimetic precipitation. Transferring

a protein from a biological silicifi cation sys-

tem to in vitro calcite precipitation led to the

formation of spicules with extremely high

fl exibility. The high quality of these spicules

allows them to be used as waveguides for

visible light.

Organisms most commonly precipitate

calcium carbonates, calcium phosphates,

or silica to produce functional hard struc-

tures. A high degree of control is required

to reproducibly form a biomineral structure

consisting of a specifi c mineral phase with a

specifi c size and morphology in the correct

location. This control is exerted by com-

plex cellular machineries in which polyan-

ionic macromolecules play a crucial role

by binding dissolved mineral constituents

and transporting them to the intended min-

eralization site in a chemically controlled

microenvironment.

Controlled biomineralization is per-

formed even by relatively simple organ-

isms such as sponges, which lack differ-

entiated tissues or organs. Most sponges

form a multitude of mineral spicules with

specifi c morphologies as an internal skel-

eton that prevents the body from collaps-

ing. Sponges can be subdivided into two

major groups: siliceous sponges producing

spicules of amorphous silica (also known

as bio-opal), and calcareous sponges that

form calcite spicules. Silica spicules are ini-

tially formed inside specialized sponge cells

where silicatein proteins catalytically medi-

ate the polymerization of silica, leading to

the formation of hydrated nanoparticles.

These particles arrange in concentric clouds

around a preformed central fi lament consist-

ing of silicatein as well ( 2). Upon condensa-

tion, a silica-silicatein composite is formed

in concentric cylindrical layers that build

up the spicule ( 3). Highly laminated silica

spicules show exceptionally high fracture

resistance because the silicatein-reinforced

layered structure counteracts catastrophic

failure through enhanced toughness and

reduced hardness, as well as through its abil-

ity to arrest microcracks ( 4).

In contrast to the silica spicules consist-

ing of noncrystalline material, calcareous

sponges produce spicules that represent

single crystals of calcite but with specifi c

elaborate morphologies, basically elon-

gated single rods or triradiate stars (see the

fi gure, panel A). Despite being well-defi ned

crystals, calcite sponge spicules contain

small amounts of polyanionic macromole-

cules incorporated within the mineral phase

( 5). These proteins presumably play a role

in the precipitation mechanism, equivalent

to that of silicatein in silica spicule for-

mation, because calcite sponge spicules

also appear to be constructed by aggrega-

tion of nanoparticles (see the fi gure, panel

B) to create smoothly curved morpholo-

gies ( 6). The proteins are assumed to tem-

porarily stabilize the particles as an amor-

phous phase of CaCO3, which then crystal-

lizes after particle aggregation into a calcite

single crystal. The granular structure with

intercalated proteins defl ects fracture prop-

agation and dissipates strain energy, reduc-

ing the brittleness of the material.

Institut für Angewandte Geowissenschaften, Technische Universität Darmstadt, 64287 Darmstadt, Germany. E-mail: sethmann@geo.tu-darmstadt.de

10.1126/science.1235591

Published by AAAS

15 MARCH 2013 VOL 339 SCIENCE www.sciencemag.org 1282

PERSPECTIVES

By crossing the systems, Natalio et al.

discovered that originally biosilica-specifi c

silicatein-α can also mediate the precipita-

tion of calcium carbonate with fi brous mor-

phology, even without biological control.

Hence, a high degree of self-assembly on the

nano- to micrometer scale must be involved

in the formation of synthetic calcite spic-

ules, and the same can be inferred for the

biomineral counterpart. Because crystallo-

graphically aligned structures are assembled

from prenucleated mineral particles instead

of “classical” ion-by-ion growth, the spic-

ules can be classifi ed as mesocrystals ( 7).

However, a peculiarity of these mesocrys-

tals is that the alignment develops only after

aggregation by conformable crystallization

of the amorphous particles, whereas nano-

crystals assemble in a crystallographically

aligned fashion from the start. Crystalliza-

tion of one particle conformably to another

one implies some semicoherence of the

crystal lattice bridging particle boundaries

despite the presence of intercalated proteins

(see the fi gure, panel C). The authors attri-

bute the extreme fl exibility of the biomi-

metic spicules to the relatively high content

of organic material, which is consistent with

mechanical studies on various biomineral

structures: Nature tunes the mechanical per-

formance of biominerals not only by varying

the microstructures but also by adjusting the

organic content ( 8).

Rarely has bioinspired mineralization

been successful in reproducing combina-

tions of advanced material properties, such

as specifi c morphology and fl exibility, in one

material. In the biomimetic fi brous calcite–

silicatein-α spicules, rubberlike toughness

and elasticity prevent fractures. The light-

guiding studies of Natalio et al. show that

the spicules go beyond biomimetic cross-

breed mineralization and enter the realm

of fl exible fi ber optics, for which smoothly

curved fi ber surfaces are a prerequisite. A

challenge for future applications will be the

elongation of these fi bers while maintaining

their microscopic width.

References 1. F. Natalio et al., Science 339, 1298 (2013). 2. W. E. G. Müller et al., Micron 37, 107 (2006). 3. X. Wang et al., Pure Appl. Chem. 82, 175 (2010). 4. A. Miserez et al., Adv. Funct. Mater. 18, 1241 (2008). 5. J. Aizenberg, M. Ilan, S. Weiner, L. Addadi, Connect. Tis-

sue Res. 34, 255 (1996). 6. I. Sethmann, R. Hinrichs, G. Wörheide, A. Putnis, J. Inorg.

Biochem. 100, 88 (2006). 7. H. Cölfen, M. Antonietti, Mesocrystals and Nonclassical

Crystallization (Wiley, Chichester, UK, 2008). 8. J. D. Currey, J. Exp. Biol. 202, 3285 (1999).

1 mm 100 nm

A B C

Increasing fl exibility with proteins. Calcareous sponge spicules and their microstructure are shown. (A) A light microscopic image reveals relatively large triactine spicules with smoothly curved surfaces. Each spic-ule represents a transparent single crystal of calcite, CaCO3. (B) Atomic force microscopic topography image of a spicule surface shows the microstructure of aggregated nanogranules. (C) Schematic drawing of a pos-sible mesocrystalline composite structure with crystallographically aligned calcite granules (brown) and inter-calated proteins (green) that leads to greater fl exibility with increasing organic content. The sponge sample was provided by G. Wörheide, Ludwig-Maximilians-Universität, München.

RNA That Gets RAN in Neurodegeneration

NEUROSCIENCE

J. Paul Taylor

A common neurodegenerative disease is

associated with unconventional translation

of mutant expanded RNA.

Amyotrophic lateral sclerosis (ALS)

and frontotemporal dementia

(FTD) are devastating neuromus-

cular and cognitive diseases, respectively,

with substantial clinical, genetic, and neu-

ropathological overlap ( 1). Mutation in the

gene C9orf72 is the most common genetic

defect underlying these two diseases ( 2, 3).

On page 1335 of this issue, Mori et al. ( 4)

report that a “repeat expansion” mutation in

C9orf72 causes an unusual defect in RNA

metabolism that may contribute to ALS,

FTD, and other neurological disorders.

The pathogenic mutation in C9orf72 con-

sists of a hexanucleotide repeat expansion in

a noncoding region (intron 1) (see the fi g-

ure). Typically, normal individuals have 23

or fewer repeats [(GGGGCC)n], but aberrant

expansion can result in hundreds to thousands

of repeats. This type of mutation in C9orf72

suggests three possible disease mechanisms.

Repeat expansion might impair expression

of the gene product, as seen in the neuro-

degenerative disease Friedreich’s ataxia ( 5).

But Friedreich’s ataxia involves impairment

of both alleles and is recessively inherited.

By contrast, the dominant inheritance pat-

tern observed in C9orf72 families makes a

loss-of-function mechanism unlikely to be

the sole cause of disease.

A more favored mechanism is RNA-

mediated toxicity. Presence of a noncoding

repeat expansion and nuclear foci of RNA

( 2) in C9orf72-related disease are reminis-

cent of traits in myotonic dystrophy types

1 and 2 ( 6). In these disorders, character-

ized by progressive dementia, myopathy,

and myotonia, RNA-binding proteins (of

the muscleblind-like family) associate with

repeat-expanded RNA, leading to abnor-

mal RNA splicing, which underlies cer-

tain clinical features. RNA-binding pro-

teins that bind to (GGGGCC)n repeats have

been identified as well ( 7). Interestingly,

among these were heterogeneous nuclear

ribonucleoprotein A1 (hnRNPA1) and

hnRNPA2B1, both recently identifi ed as dis-

Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA. E-mail: jpaul.taylor@stjude.org

10.1126/science.1235357

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