CHARACTERIZING LIQUID-ORDERED AND LIQUID-DISORDERED PHASE PROPERTIES AND INTERFACES
Specialized lipid microdomains, or "membrane rafts", are thought to be involved in many plasma membrane events like signaling, protein sorting, and viral entry and exit. The size and dynamics of membrane domains is governed by the energy penalty for domain interface, called line tension, making it an important quantity in the discussion of compartmentalization of functions for signaling at the plasma membrane via possible phase separation. Cells must also be able to maintain and change membrane shape. Curvature of the membrane can be influenced by lateral heterogeneities as well as a means to induce lateral heterogeneity. Thus both the line tension and membrane bending rigidity are important quantities for understanding “raft” behavior. Mixtures of high-melting lipid, low-melting lipid(s), and cholesterol exhibit a region of liquid-ordered (Lo) + liquid-disordered (Ld) phase coexistence analogous to raft + non-raft behavior in cells. Line tension depends strongly on the lipids comprising the mixture, with a minimal line tension required for visible phase domains to form. I have shown that line tension ,calculated in terms of pairwise lipid interactions, agrees with experimental values. I measured the bending modulus of the respective coexisting Ld and Lo phases and found that in the presence of near physiological amounts of transmembrane peptides the more ordered domains are not necessarily more rigid and may actually form highly curved structures more readily. As cholesterol is increased and the coexisting phases become more compositionally similar, I found a slight rigidifying effect of cholesterol on Ld phases and a dramatic decrease in Lo rigidity. In a model with coexisting nanoscopic phases, I found that the continuous phase determines the membrane rigidity.
Feigenson, Gerald W.
Zipfel, Warren R.; Vogt, Volker M.
Biochemistry, Molecular and Cell Biology
Ph. D., Biochemistry, Molecular and Cell Biology
Doctor of Philosophy
dissertation or thesis