Alan Grossfield, University of Rochester Medical Center

Thermodynamics of lipid phase separation using molecular simulations

Abstract:

Liquid-liquid phase separation (LLPS) inside the cell often results in biological condensates that can critically impact cell homeostasis. Such 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 this reason, simple model systems that can recapitulate similar behavior are widely used to study this phenomenon. Despite these simplifications, the timescale and length scales of domain formation pose a challenge for molecular dynamics 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 novel protocol to directly measure the free energy changes associated with membrane phase separation. This technique will allow us to forge connections between simple model of phase separation, simulations at various resolutions, and experiments.

Speaker: Alan Grossfield, University of Rochester Medical Center

Alan Grossfield is an Associate Professor in the Department of Biochemistry and Biophysics at the University of Rochester Medical Center. After receiving a Bachelor's degree in Physics from Cornell University, Dr. Grossfield completed his Ph.D. in Molecular Biophysics at Johns Hopkins Medical Center, where he investigated protein-lipid interactions under the guidance of Dr. Thomas Woolf. He then pursued a postdoctoral fellowship at Washington University Medical School, focusing on the solvation of ions using polarizable force fields with Dr. Jay Ponder. In 2004, Dr. Grossfield joined the IBM TJ Watson Research Center as a research staff member, working on simulations of rhodopsin and lipid-protein interactions. Dr. Grossfield joined the faculty at the University of Rochester Medical Center in 2007, where he continues his research in computational biophysics.

Host: Jason Kahn

Seminars start at 4:00 pm, and refreshments will be served at 3:45 pm. All seminars are held in the Conference Room (1116) of the Institute for Physical Science and Technology (IPST) Building (Bldg #085) unless otherwise noted.