title: Membrane bending by protein crowding is affected by protein lateral confinement.
abstract: Crowding of asymmetrically-distributed membrane proteins has been recently recognized as an important factor in remodeling of biological membranes, for example during transport vesicle formation. In this paper, we theoretically analyze the effect of protein crowding on membrane bending and examine its dependence on protein size, shape, transmembrane asymmetry and lateral confinement. We consider three scenarios of protein lateral organization, which are highly relevant for cellular membranes in general: freely diffusing membrane proteins without lateral confinement, the presence of a diffusion barrier and interactions with a vesicular coat. We show that protein crowding affects vesicle formation even if the proteins are distributed symmetrically across the membrane and that this effect depends significantly on lateral confinement. The largest crowding effect is predicted for the proteins that are confined to the forming vesicle by a diffusion barrier. We calculate the bending properties of a crowded membrane and find that its spontaneous curvature depends primarily on the degree of transmembrane asymmetry, and its effective bending modulus on the type of lateral confinement. Using the example of COPII vesicle formation from the endoplasmic reticulum, we analyze the energetic cost of vesicle formation. The results provide a novel insight into the effects of lateral and transmembrane organization of membrane proteins, and can guide data interpretation and future experimental approaches.
authors.affiliation: Institute of Biophysics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. Electronic address: jure.derganc@mf.uni-lj.si.
authors.forename: Jure
authors.initials: J
authors.lastname: Derganc
authors.affiliation: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France. Electronic address: alenka.copic@ijm.fr.
authors.forename: Alenka
authors.initials: A
authors.lastname: Čopič
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008954:Models, Biological
chemical_list: D008565:Membrane Proteins
keywords: Membrane bending; Membrane diffusion barrier; Membrane protein asymmetry; Protein crowding; Vesicle formation