Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Thursday Speaker Abstracts

EXPANDING COARSE-GRAINED MODEL FOR LIPIDS TO INVESTIGATE LO/LD PHASE COEXISTENCE Malavika Varma 1 ; Markus Deserno 1 ; 1 Carnegie Mellon University, Dept. of Physics, Pittsburgh, PA, USA Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins that are widely believed to underlie the experimentally well-established lateral heterogeneity of eukaryotic plasma membranes. Membrane rafts function as signaling platforms in diverse cellular processes, such as immune regulation, cell cycle control, membrane trafficking and fusion events. The coexistence of distinct fluid phases, particularly the liquid ordered (Lo) and liquid-disordered (Ld) phases, is considered to be a highly plausible model for raft formation. Additionally, cholesterol significantly influences this process by modulating membrane fluidity, permeability, lipid packing, and protein mobility. We have expanded the Cooke model for lipids, a highly coarse-grained model extensively utilized for exploring membrane mechanics, so that it can explore the physics of Lo/Ld phase coexistence, thereby introducing the thermodynamics of mixtures into the model. Our model simplifies a complex system and captures its large-scale physics, helping us to explore the interplay of membrane mechanics and phase behavior. In particular, we outline the phase diagram roughly and estimate the location of the critical point, shedding light on the system's thermodynamic state. In addition, we measure observables such as membrane area expansion modulus (KA) and lipid diffusion constants, uncovering trends like anti-registered domains and increased KA with reduced phase separation. Because Lo/Ld phase behavior relies on leaflet cholesterol fraction, which in turn is sensitive to differential stress [Varma & Deserno, BiophysJ 2022], adjusting lipid packing in the inner leaflet enables us to control raft formation in the outer leaflet. We leverage the capabilities of our simulation model to apply differential stress to membranes exhibiting Lo/Ld phase coexistence, thus obtaining valuable insight into the interplay between various types of asymmetries and membrane phase behavior.

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