1. Lecture 17: Lipid Vesicles and Membranes

2. What did we cover in the last lecture? Amphiphilic molecules contain a hydrophobic head group and hydrophobic tail group. When added to water in they form micelles above a critical concentration. Their shape is determined by the volume and length of the tail and the optimum area of the molecular headgroups. A geometric packing parameter can be used to identify whether spherical, cylindrical or bilayer structures will form. Hydrophilic head groups Hydrophobic tail groups

3. In this lecture… 1) Lipids 2) Bilayers revisited 3) Lipid Vesicles 4) Curvature of lipid membranes Further Reading Intermolecular and Surface Forces J. Israelachvili, p378 - 385

4. Amphiphile shapes In the last lecture we saw that the shape of micelles formed by amphiphiles is determined by a geometric packing parameter Small v Large l c and a o Large v Small l c and a o lclc Area a o Volume v

5. Lipid bi-layers Lipids are naturally occurring amphiphiles. They have two short, bulky hydrocarbon chains This means that l c is small, but v is quite large. They therefore have a tendency to form bi-layer structures. Phosphatidylcholine (PC) is a phospholipid that is one of the main constituents of all animal cell membranes

6. Vesicle formation When lipid bi-layers are formed in solution, there is an excess energy associated with the exposed hydrophobic tail groups at the edges of the structure The bi-layers can offset this energy by folding around to close themselves off and form an isolated shell or vesicle vesicle

7. Applications of vesicles Vesicles are closed structures and can be used to encapsulate materials in their interior for use in drug delivery If the outside of the vesicle is decorated with specific chemical receptors which cause the vesicle to rupture when it reaches its target it can act like a ‘magic bullet’ They are also an excellent model of mammal cells for use in biophysics experiments http://www.youtube.com/watch?v =04SP8Tw3htE

8. Curvature of membranes Curvature of membranes introduces constraints into the way in which amphiphiles can pack in a membrane. It also varies the headgroup separation of lipids and thus has an energy penalty associated with it (just like bending a sheet of material). Smaller radii of curvature require more bending energy. These constraints result in a minimum radius of curvature below which vesicles cannot form. (See OHP)

9. How does R vary with l ? As the length of the hydrocarbon chain increases, the radius decreases R takes its minimum value when the hydrocarbon chain is fully stretched. i.e. when l=l c

10. Geometric packing parameters (again) Our expression for the minimum radius of curvature of a vesicle forces us to reinterpret the range of values of H for which bilayers and vesicles will form It is clear that any bi-layer will tend to try to curve up on itself to eliminate unfavourable hydrophobic/water contacts When H=1, R c = ∞, so perfectly flat bi-layers will form When R c is finite and vesicles will form

11. Problem Calculate the minimum radius of curvature of vesicles made from egg phosphatidylcholine which has measured headgroup area and hydrocarbon volume of 0.717 nm 2 and 1.063 nm 3 respectively, if the critical chain length for this lipid is 1.75nm Calculate an estimate of the number of lipid molecules in the vesicle wall

12. Summary of key concepts Lipid/amphiphile bilayers will tend to close up to form vesicles to eliminate unfavourable hydrophobic contacts Geometrical constraints and the energy penalty associated with bending the membranes places a lower limit on the radius of vesicles Vesicles are excellent models of cell membranes and can be used for targeted delivery of drugs and other chemicals