Theoretical and Computational Studies of the Lateral Phases on a Multicomponent Lipid-Bilayer Surface

Abstract

The lipid-bilayer membrane is the fundamental structure of a cell plasma membrane and has been largely studied by biophysical experiments, theoretical modeling and computer simulations. Two major aspects of lipid bilayer morphologies are studied, namely lateral phase separation and pattern formation (spatial organization of lipid molecules), and shape change or deformation of the membrane (undulation of the surface). In this dissertation, I apply theoretical modeling, analytical and numerical computation as well as molecular simulation to study the lateral phases on the surface of a multicomponent lipid bilayer, which is able to stay in a homogeneous state, phase separate, or transform into heterogeneous states including modulated phases and microemulsions. The focal point is a lipid-bilayer vesicle of finite size and spherical topology. I calculate phase diagrams which reveal the effects of intrinsic finite sizes of vesicles on their surface pattern and lateral phase generation. I also calculate the structure factor of vesicles, which is measured by scattering signals, and theoretically develop an approximate model-independent interconversion between the three-dimensional signal and the two-dimensional structure factor of planar membranes, and I also stress the finite size effect in this relation. It is also observed that the lipid domain formation is coupled with membrane curvature distribution on the surface. I apply the coupling through domain bending properties, and create phase diagrams in which changing membrane mechanical properties can vary the lateral phases on a vesicle surface. In addition to the aforementioned continuum modeling, I also utilize coarse-grained molecular dynamics simulation to explore the phase behavior of asymmetric lipid bilayers consisting of a phase-separating leaflet and a homogeneous leaflet, in which the former would induce a tendency of phase separation in the latter. The molecular simulation, which keeps a record of each lipid molecule, could be a more biologically relevant model of plasma membranes.