Asymmetric Membrane Models for the PM And TGN of Yeast, An All-Atom Molecular Dynamics Study

Abstract

We previously examined symmetric membrane models for the plasma (PM) and trans-Golgi-network (TGN) membranes of Saccharomyces cerevisiae (yeast) (Biochem 54:6852-6861). Although diverse in lipid nature and reflecting sterol compositions characteristic to those organelles, our models were not an accurate enough representation as they lacked sphingolipids (SM), relevant for membrane structure and dynamics. Once SM were parametrized for the CHARMM 36 lipid force field (BJ, 107:134-145), we included them in the new models and added lipid composition asymmetry to better reflect the complexity of these bilayers. The new models include inositol phosphoceramide (IPC) and mannose-(inositol-P)2-ceramide M(IP)2C lipids, both present in the non-cytosolic leaflets of the PM and TGN. We present a comparison study between the previous PM model and the more complex ones using common membrane properties such as surface area per lipid, bilayer thickness, deuterium order parameters, lipid diffusion constants, and lipid cluster formation. The last three properties will serve to investigate lipid phase coexistence and leaflet coupling in membrane order and diffusion. Our simulation trajectories were at least 2µs long for each of the three models (old-PM, PM, and TGN), for a total of 15 µs of simulation data run in the Anton machine at the Pittsburgh Supercomputing Center.