SMBp Seminar: Alan Grossfield (University of Rochester Medical Center)

Thursday Aug 15, 2024, 11:00 AM → 12:00 PM America/New_York

3rd Floor Classroom (162 Fifth Avenue)

Speaker: Alan Grossfield (University of Rochester Medical Center)

Title: Understanding the thermodynamics of phase separation in lipid membranes using molecular simulations

Abstract: Liquid-liquid phase separation and the resultant formation of biological condensates plays an essential role in cellular function. Phase separation was first characterized in a biological context as the "lipid raft" hypothesis describing the mixing behavior of cellular membranes. Various experiments dating back to the 1980s and 90s robustly demonstrated that certain lipid mixtures form distinct phases, and temperature-dependent phase diagrams have been determined for many lipid mixtures. Simultaneously, advances in computer power and coarse-grained modeling techniques have made it possible to model the phase separation process directly. Despite these efforts, the molecular grammar that controls phase separation is not well understood from a thermodynamic perspective. One major challenge is these approaches reveal the stable configuration of the system, but provide no information about precisely how stable that state is. As a result, changes to the system that alter the favorability of phase separation without changing the sign of the free energy change are invisible.  To meet this need, we have developed a novel technique using molecular dynamics simulations to directly assess the free energy changes associated with forming coexisting phases in lipid bilayers, built around the weighted ensemble method.  We demonstrate that the method is effective and apply it to determine the dependence of phase separation on the size of the system simulated.