Soft Matter/ (PoLS) Seminar - Prof. Alan Grossfield

Speaker: Prof. Alan Grossfield

Host: Prof. JC Gumbart

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

Abstract:

Phase separation occurs in multiple parts of cells, including the cell membranes, where the so-called ``lipid raft'' hypothesis posits the formation of ordered domains floating in a sea of disordered lipids. The resulting lipid domains often have functional roles. However, the thermodynamics of lipid phase separation and their resulting mechanistic effects on cell function and dysfunction are poorly understood. Understanding such complex phenomena in cell membranes, with their diverse lipid compositions, is exceptionally difficult. For these reasons, simple model systems that can recapitulate similar behavior are widely used to study this phenomenon. Despite these simplifications, the time- and length-scales of domain formation pose a challenge for molecular dynamics (MD) simulations. Thus, most MD studies focus on spontaneous lipid phase separation --- essentially measuring the sign (but not the amplitude) of the free energy change upon separation --- rather than directly interrogating the thermodynamics.  We have developed a set of techniques to extract the free energy change upon phase separation directly from molecular dynamics simulations. In addition to a number of validation studies, we have used these methods to determine the simulation size needed to recapitulate the thermodynamics of membrane phase separation.