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Biophysics IIBiophysics II

ByByA/Prof. Xiang Yang LiuA/Prof. Xiang Yang LiuDepartment of Physics, Department of Physics, NUSNUS

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Outline

1. The environment in the cell 2. Hydrophilic vs hydrophobic and

amphiphlic molecules self assembly :

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Cell and biomenbraneThe four essential parts of cell:

•Nucleus,

•Cytoplasm,

•Organelles,

•Membrane

• In order to keep cells alive and function properly, the intracellular condition is different from extra cellular conditions.

• How about biomembrane?

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Structure and Function:The Phospholipid Bilayer

The plasma membrane is common to all cellsSeparates:

Internal living cytoplasmic fromExternal environment of cell

Phospholipid bilayer:External surface lined with hydrophilic polar headsCytoplasmic surface lined with hydrophilic polar headsNonpolar, hydrophobic, fatty-acid tails sandwiched in between

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Cell and biomenbrane (cont’d)

Biomembrane: Lipid Bilayer

Semi-ordered Liquid!

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Membrane Models

Fluid-Mosaic ModelThree components:

Basic membrane referred to as phospholipid bilayerProtein molecules

Float around like icebergs on a seaMembrane proteins may be peripheral or integral

Peripheral proteins are found on the inner membrane surfaceIntegral proteins are partially or wholly embedded (transmembrane) in the membrane

Some have carbohydrate chains attachedCholesterol

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Membrane Models:Unit Membrane vs. Fluid Mosaic Model

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The Fluid Mosaic Model

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Phospholipid & Cholesterol Molecules

Hydrophilic head: O, S, N,… Hydrophobic tails: H, C,…Charged, polar groups

Non- polar/ weak polar groups

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Functions of Membrane ProteinsChannel Proteins:

TubularAllow passage of molecules through membrane

Carrier Proteins:Combine with substance to be transportedAssist passage of molecules through membrane

Cell Recognition Proteins:Provides unique chemical ID for cellsHelp body recognize foreign substances

Receptor Proteins:Binds with messenger moleculeCauses cell to respond to message

Enzymatic Proteins:Carry out metabolic reactions directly

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Membrane Protein Diversity

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Self-Assembly in Cells

Questions: How can amphiphilic molecules satisfy their hydrophobic tails in a pure water environment? How do the amphiphilic molecules assemble in an aqueous solution?How do amphiphilic molecules are packed into different shapes of aggregates

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Amphipathic (Amphiphilic) MoleculesBoth hydrophilic and hydrophobic

A hydrophobic part

A hydrophilic part

Hydrophobic vs hydrophilic force

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Amphiphilic moleculesTwo classes of amphiphiles. (a) Structure of sodium dodecyl sulfate (SDS), a strong detergent. A nonpolar, hydrophobic, tail (left) is chemically linked to a polar, hydrophilic head (right). In solution, the Na+ ion dissociates. Molecules from this class form micelles. (b) Structure of a generic phosphatidylcholine, a class of phospholipid molecule. Two hydrophobic tails (left) are chemically linked to a hydrophilic head (right). Molecules from this class form bilayers.

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Self-assembly

Self-assembly: appropriate molecules gather together spontaneously to assemble into some entities of certain structures.What is the driving force behind it?

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Driving force for amphiphilic molecular self-assembly

Optimal interaction/packing for amphiphilicmolecules:

Hydrophobic region in contact with hydrophobic regionhydrophilic region in contact with hydrophilic regionhydrophilic region avoiding hydrophilic region

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Amphiphilic molecule self-assembly at the interface

Hydrophobic-hydrophobic

Hydrophilic-hydrophilic

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Amphiphilic molecule self-assembly at the interface

Lower surface (interfacial) tension

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air

water

oil

water

High surface (interfacial) tension

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Surface tensiometer to measure the surface tension

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CMCLower the surface tension

Micelles self-assemble suddenly at a critical concentration (Critical Micellization Concentration-CMC)

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Bilayers self-assemble from two tailed amphiphiles

Amphipathic (Amphiphilic) Molecules

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Self -assembly of amphiphilies

Assembly of amphiphilic molecules at the interface will reduce the interracial tension

At the water surface- reduce the surface tension.

What happens after CMC?Assembly into different shapes of micelles

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Self-assembly

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Micelle solution

MicelleAt C > CMC

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Aggregates results from molecular self assembly

How can these aggregates be built into different shapes?

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Hydrophobic forces:Van der WaalsStericConfigurational…

Hydrophilic forces:ElectrostaticPolar-polarHydrogen bond…

stail shead

stail > shead

stail = shead

stail < shead

U(r)

r

0

Virtual Diameter

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The optimal intermolecular interactions correspond to optimal “packing” of these molecules, which leads to the self assembly of molecules into different shapes.

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Spherical

P <13

Rod-like

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≤ ≤P

Disk-like

1~P

Perfect balance of hydrophobic and hydrophilic forces

Due to different physical forces, amphiphilic molecules will self assemble into aggregates with different shapes

s

l

v

P = stail / shead

Bilayer

stail = v/l

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Emulsion form when amphiphlic molecules reduce the oil-water interfacial tension

(a) An oil–water interface stabilized by the addition of a small amount ofsurfactant. Some surfactant molecules are dissolved in the bulk oil or water regions, but mostmigrate to the boundary as shown in the inset. (b) An oil–water emulsion stabilized by surfactant:The situation is the same as (a), but for a finite droplet of oil.

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Micellization- A special type of phase transition

N monomers ⇔ One aggregate (N-mer)

CN/C1N = Keq

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Self-Assembly in cellsTo form micelles, the volume NVtail occupied by the tails of N

surfactants must be compatible with the surface area Nahead occupied by the heads for some N.Suppose that N amphiphiles pack into a spherical micelle of radius R. Find two relations between ahead, Vtail, R, and N. Combine these into a single relation between ahead, Vtail, and R.Suppose instead that amphiphiles pack into a planar bilayer of thickness 2d. Find a relation between ahead, Vtail, and d. Suppose instead that amphiphiles pack into a planar bilayer of thickness 2d. Find a relation between ahead, Vtail, and d.Why are one-tail amphiphiles likely to form micelles, whereas two-tail amphiphiles are likely to form bilayers?

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Why phospholipid?Why Nature has chosen the phospholipid bilayer

membrane as the most ubiquitous architectural component of cells: The self-assembly of two-chain phospholipids (like PC) into bilayers is even more avid than that of one-chain surfactants (like SDS) into micelles. Chemical drive for self-assembly: This free energy cost εenters the equilibrium constant and hence the CMC. A big difference between e-ε/kT (single chain) and e-2ε/kT

(double chain). -The CMC for phospholipid formation is tiny. Membranes resist dissolving even in environments with extremely low phospholipid concentration.

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Why phospholipid?Similarly, phospholipid membranes automatically form bilayervesicles which , can be almost unlimited in extent; it is straightforward to make “giant” vesicles of radius 10 μm, the size of eukaryotic cells. Phospholipids are not particularly exotic or complex molecules. They are relatively easy for a cell to synthesize.Unlike, say, a sandwich wrapper, bilayer membranes are fluid. No specific chemical bond connects any phospholipid molecule to any other, just the generic dislike of water for the hydrophobic tails. This fluidity makes it possible for membrane-bound cells to change their shape.

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Membrane-Assisted Transport:Exocytosis

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Membrane-Assisted Transport:Three Types of Endocytosis

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Why phospholipid?Because of the nonspecific nature of the hydrophobic interaction, membranes readily accept embedded objects; hence they can serve as the doorways to.

Solubilization of integral membrane proteins (black blobs) by detergent (objects with shaded heads and one tail).

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Review

Self assembly of amphiphilc molecules CMCPacking parameter and shapeKey characteristics of phospholipid bilayer

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Reference

Chapter 8 in Biological physicsChapter 1, D. Fennell Evans, HakanWennerstrom, The Colloidal Domain where physics, chemistry, biology, and Technology Meet, VCH, 1994