Theory of Liquid-Liquid Phase Separation in Model Lipid Bilayers

This thesis presents phenomenological and theoretical work related to phase separation in fluid lipid bilayers. We describe a phenomenological model which explains the liquid-liquid phase behavior of the ternary mixture DPPC/diphytanoylPC/cholesterol on the basis of interactions between these components, which depend on the extent of orientational order of the saturated lipid acyl chains. An extension of this model to include complexes of lipids illustrates the effect on phase behavior of chemical crosslinking via a reduction of mixing entropy, which could explain the experimentally observed phenomenon of crosslinking-induced phase separation. We also present a phenomenological model of lipid bilayers with coupled leaflets that describes the conditions under which compositionally asymmetric bilayers undergo phase separation. This model reproduces several experimental observations. We also analyze the fluctuations of phase domain boundaries in phase-separated bilayers with coupled leaflets, showing how the interleaflet coupling energy relates to the spatial extent of areas of mismatch between the states of the apposing leaflets. We estimate the magnitude of this interleaflet coupling on the basis of the molecular mean-field model developed by Elliott et al. Finally, we examine the possibility that the presence of lipids with electrically charged head groups in the inner leaflet of the cell plasma membrane leads to compositional fluctuations with a characteristic spatial extent. By calculating the effect of electrostatic interactions on the spectrum of compositional fluctuations, we derive a criterion by which this characteristic length is manifest in the structure function.