Lipid Membranes: From Organizational Strategies in Cells to the Origins of Life

Abstract

Lipids, a fundamental building block of cells, can spontaneously self-assemble into vesicles, which are spherical shells consisting of a lipid bilayer. The structure of lipid bilayers determines their biological function: membranes are elastic, selectively permeable, and fluid barriers that separate the internal components of a cell from its external environment. Historically, the cell membrane has been viewed as a passive medium in which biologically active proteins reside. In the past several decades, investigation of the unique physical properties of multi-component lipid bilayers has uncovered the active organizational role of lipids in the cell membrane. Through changes in temperature or lipid composition, model ternary lipid bilayers can phase separate into coexisting liquid phases. Similarly, the membrane of living unperturbed yeast vacuoles exhibits coexisting liquid phases under stress conditions. Lipid membranes also have a role in the origins of cellular life: prebiotically-feasible bilayers concentrate the building blocks of protein and RNA, catalyzing the formation of biological polymers. This text describes some physical properties of lipid membranes and their role in biological organization and the origins of cellular life. The chapters of this thesis start with (1) an introduction and then explore (2) the effect of general anesthetics on the phase behavior of synthetic and cell-derived membranes, (3) periodic small domains in synthetic and cell-derived membranes, (4) coexisting liquid phases on the submicron scale using cryo electron tomography, (5) miscibility transition temperatures of living, unperturbed yeast vacuole membranes, and (6) binding and stabilization of prebiotic fatty acid membranes by prebiotic amino acids. These examples demonstrate the importance of lipid membranes across many aspects of biology and the power of simple physical principles to explain complex phenomena.