α-Synuclein Induced Membrane Curvature: What is the Significance of Negative Gaussian Curvature

Abstract

α-Synuclein (αS) is an intrinsically disordered protein that forms an amphipathic α-helix upon binding to lipid vesicles. Using Molecular Dynamics simulations we have recently shown that the protein induces an anisotropic curvature field in the phospholipid bilayer when bound to a membrane. First, as is known to be characteristic of amphipathic helices, αS induces positive mean curvature (a hill). More interestingly, our simulations suggested unexpected complexities in the induced Gaussian curvature field. Our current efforts, described here, explore the physical principles that dictate these membrane curvature features, again using large-scale simulations. Our focus has been on how three physical aspects of the protein (helix length, flexibility, and hydrophobicity) lead to these complex curvature fields. In addition, we explore the relationship between negative Gaussian curvature and membrane tubulation.