Fluctuating Lipid Membranes: Structure, Non-equilibrium Dynamics, and Coupling to Membrane Proteins

Princeton University, Princeton NJ

Investigators

Abstract

TECHNICAL SUMMARY This award supports theoretical studies and education at the intersection between condensed matter physics, computational materials science, and membrane biophysics. The projects focus on spatial organization, regulation, and non-equilibrium dynamics of heterogeneous, multicomponent lipid bilayer membranes. Lipid membranes are ubiquitous in mammalian cells, and facilitate the interaction between a cell and its surroundings. Furthermore, lipid membranes are employed in important biomedical applications, such as vehicles for targeted drug delivery. Notably, membrane "microstructure" might arise, for example, from local lipid and protein compositions, and directly controls the mechanical, physical, and biochemical properties of the system. The PI aims to develop and employ effective, coarse-grained Ginzburg-Landau models for materials behavior across several length scales. These continuum and hybrid particle-continuum models will be employed to address several key questions, including: (1) What are the roles of membrane and exterior solvent hydrodynamics on lipid microdomain formation kinetics? (2) How do the lipid microdomains associate/aggregate? How important are protein-lipid interactions in microdomain aggregation? (3) How are spatio-temporal correlations in the underlying lipid composition fields reflected in reporter particle correlations? Can we devise methods, which facilitate the quantification of sub-micron lipid microdomain structure and correlations from experimental data? (4) What are the effects of spontaneous or induced membrane curvature on lipid raft formation and stability? (5) How are the lipid compositions coupled across the two leaflets? How does this coupling affect lipid microdomain formation and stability? In the short term, these studies will lead to a better understanding of nonlinear pattern formation and self-organization processes on molecular and mesoscopic scales in biological systems and biomaterials. In the long term, these research and educational activities will (1) contribute to the training of the next generation of scientists at the intersection between condensed matter physics, materials science, and biology, and (2) pave the way for a more fundamental understanding of the role of compositional lipid domains in cellular signaling and trafficking, with potential impact in biophysics, cellular biology, biomaterials, and medicine. NONTECHNICAL SUMMARY This award supports theoretical studies and education at the intersection between condensed matter physics, computational materials science, and membrane biophysics. Lipid bilayer membranes are ubiquitous in mammalian cells, and facilitate the interaction between a cell and its surroundings. Furthermore, lipid membranes are employed in important biomedical applications, such as vehicles for targeted drug delivery. Like more traditional materials, such as metals and alloys, the structure of a membrane on length scales longer than the distance between atoms and molecules, but still less than the size of cells, directly controls the mechanical, physical, and biochemical properties of the membrane. The PI will study this microstructure of lipid membranes. He will develop models that are accessible to modern computers and can capture the effects of membrane microstructure in both synthetic and natural lipid bilayer membranes. The PI aims to advance our fundamental understanding of evolving microstructures in live cells and biomaterials. This will contribute to a better understanding of how molecules and membranes organize themselves in biological systems and materials. In the long term, these research and educational activities will (1) contribute to the training of the next generation of scientists at the intersection between condensed matter physics, materials science, and biology, and (2) pave the way for a more fundamental understanding of the role of lipid microstructure in cellular function with potential impact in biophysics, cellular biology, biomaterials, and medicine.