Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Chapter 5 of Yeagle Structure of Biological Membranes•Non-lamellar phases •Spontaneous curvature•Actual curvatureWhat 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 compositionIn cells, primarily lamellar structures are found, yet lipids extracted from cells will form non-lamellar phases in vitro.•POLYMORPHISM•MESOMORPHISMGeneral 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 chemistryThis 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•organellesX-ray diffraction and NMREPR, UV-VIS, IR, Calorimetry, Neutron diffractionGOAL: INTUITIVE UNDERSTANDING OF THE FORCESTHAT DRIVE THE FORMATION OF CURVATURE ALTERING PHASE TRANSITIONSTERMINOLOGY:•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 domainOIL-WATER SURFACTANT MICELLESWhat happens when you have detergents and a small amount of oil in water?What happens when the oil is the majority constituent?THERMOTROPISM and LYOTROPISMPhenomenological 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 playFor 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/RoCo = spontaneous curvatureRo = radius of spontaneous curvatureRigidity of objectE = 0 when R = R0Parabolic dependencePerform X-ray crystallography and obtain d-spacing and reflectionsBy adding 16%(w) tetradecane, it is possible to minimize the unfavorable packing of the acylchains, thus lowering the phase transition temperature to the hex phaseAs you raise the Temperature, the tube radius becomes smallerInverted Hex phase is a cylinderBending membranes using:1) Lipids themselves2) Molecular motors3) Protein bindingBending 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 proteinsLocal 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
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