Chapter 5 of Yeagle Structure of Biological Membranes

•Non-lamellar phases •Spontaneous curvature•Actual curvature

What is the physical basis of non-lamellar phase structures? Can we understand the competing forces that stabilize a lamellar versus a non-lamellar phase?

Bilayer thicknessSurface chargeDielectric constantLipid composition

In cells, primarily lamellar structures are found, yet lipids extracted from cells will form non-lamellar phases in vitro.

•POLYMORPHISM•MESOMORPHISM

General Motivation: (1) by studying structural polymorphism/mesomorphism, one gaines an understanding of the forces that are “locked-up” in biomembranes that can affect the organization and function of membrane proteins

(2) Generally extended to surfactant/detergent chemistry

This chapter is interested in phase changes that change the CURVATURE of the lipid-water interface.These phases occur at temperatures above the gel-liquid transition, but below the transition temperature to an isotropic liquid.

Why do we care about CURVATURE?

•Cell division•Endocytosis•Membrane fusion•Structure•organelles

X-ray diffraction and NMR EPR, UV-VIS, IR, Calorimetry, Neutron diffraction

GOAL: INTUITIVE UNDERSTANDING OF THE FORCESTHAT DRIVE THE FORMATION OF CURVATURE ALTERING PHASE TRANSITIONS

TERMINOLOGY:•NON-BILAYER PHASE: really means non-lamellar, but still a bilayer of phospholipids•INVERTED/WATER-IN-OIL PHASE: HII phase, possess a net concave curvature when viewed from the water domain.•NONINVERTED/OIL-IN-WATER PHASE: HI phase, possesses a net convex curvature when viewed from the water domain

OIL-WATER SURFACTANT MICELLES

What happens when you have detergents and a small amount of oil in water?What happens when the oil is the majority constituent?

THERMOTROPISM and LYOTROPISM

Phenomenological Approach: like Hooke’s Law – the force required to stretch an elastic object is linearly proportional to displacement from equilibrium position.

This disregards the molecular forces at play

For lipid bilayers: the fundamental unit of all lipid mesomorphs is the lipid monolayer, and that this monolayer may be endowed with a spontaneous tendency to curl.

Co = 1/Ro

Co = spontaneous curvatureRo = radius of spontaneous curvature

Rigidity of object

E = 0 when R = R0

Parabolic dependence

Perform X-ray crystallography and obtain d-spacing and reflections

By adding 16%(w) tetradecane, it is possible to minimize the unfavorable packing of the acylchains, thus lowering the phase transition temperature to the hex phase

As you raise the Temperature, the tube radius becomes smaller

Inverted Hex phase is a cylinder

Bending membranes using:1) Lipids themselves2) Molecular motors3) Protein binding

Bending by proteins:

Scaffolding Mechanism The protein coats that cover budding membrane surfaces function as “scaffolds” to curve the membrane. Constraint is that protein must be curved and rigid for the membrane to “follow”. There must also be a tight binding examples: dynamin and BAR-domain proteins

Local Spontaneous Curvature Mechanism. Spontaneous curvature is generated by the penetration of a protein into the membrane.Example is the ENTH domain of epsin. It is involved in clathrin mediated endocytosis. The ENTH domain binds to PIPs (PI-4,5 biphosphate)

Amphiphysin is another protein example. Both have amphipathic helices that insert into the bilayer which may cause a local curvature strain.

Sensing by proteins:

A new concept in cell trafficing and membrane curvature is that proteins can sense curvature.

Proteins have been discovered that have binding affinities that are dependent upon the radius of membrane curvature.