title: Curvature-undulation coupling as a basis for curvature sensing and generation in bilayer membranes.
abstract: We present coarse-grained molecular dynamics simulations of the epsin N-terminal homology domain interacting with a lipid bilayer and demonstrate a rigorous theoretical formalism and analysis method for computing the induced curvature field in varying concentrations of the protein in the dilute limit. Our theory is based on the description of the height-height undulation spectrum in the presence of a curvature field. We formulated an objective function to compare the acquired undulation spectrum from the simulations to that of the theory. We recover the curvature field parameters by minimizing the objective function even in the limit where the protein-induced membrane curvature is of the same order as the amplitude due to thermal undulations. The coupling between curvature and undulations leads to significant predictions: (i) Under dilute conditions, the proteins can sense a site of spontaneous curvature at distances much larger than their size; (ii) as the density of proteins increases the coupling focuses and stabilizes the curvature field to the site of the proteins; and (iii) the mapping of the protein localization and the induction of a stable curvature is a cooperative process that can be described through a Hill function.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Bradley
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104 rradhak@seas.upenn.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Radhakrishnan
mesh_terms: D000465:Algorithms; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins
keywords: coarse-grained molecular dynamics; curvature-inducing proteins; equipartition; fluctuation analysis; membrane undulations