title: Flexible charged macromolecules on mixed fluid lipid membranes: theory and Monte Carlo simulations.
abstract: Fluid membranes containing charged lipids enhance binding of oppositely charged proteins by mobilizing these lipids into the interaction zone, overcoming the concomitant entropic losses due to lipid segregation and lower conformational freedom upon macromolecule adsorption. We study this energetic-entropic interplay using Monte Carlo simulations and theory. Our model system consists of a flexible cationic polyelectrolyte, interacting, via Debye-Hückel and short-ranged repulsive potentials, with membranes containing neutral lipids, 1% tetravalent, and 10% (or 1%) monovalent anionic lipids. Adsorption onto a fluid membrane is invariably stronger than to an equally charged frozen or uniform membrane. Although monovalent lipids may suffice for binding rigid macromolecules, polyvalent counter-lipids (e.g., phosphatidylinositol 4,5 bisphosphate), whose entropy loss upon localization is negligible, are crucial for binding flexible macromolecules, which lose conformational entropy upon adsorption. Extending Rosenbluth's Monte Carlo scheme we directly simulate polymer adsorption on fluid membranes. Yet, we argue that similar information could be derived from a biased superposition of quenched membrane simulations. Using a simple cell model we account for surface concentration effects, and show that the average adsorption probabilities on annealed and quenched membranes coincide at vanishing surface concentrations. We discuss the relevance of our model to the electrostatic-switch mechanism of, e.g., the myristoylated alanine-rich C kinase substrate protein.
authors.affiliation: Department of Physical Chemistry and The Fritz Haber Research Center, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Shelly
authors.initials: S
authors.lastname: Tzlil
authors.forename: Avinoam
authors.initials: A
authors.lastname: Ben-Shaul
mesh_terms: D000327:Adsorption; D000409:Alanine / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D002412:Cations; D002462:Cell Membrane / Q000737:chemistry; D003198:Computer Simulation; D004058:Diffusion; D004573:Electrolytes; D019277:Entropy; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry; D015233:Models, Statistical; D009010:Monte Carlo Method; D019814:Myristic Acid / Q000737:chemistry; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D002412:Cations; D004573:Electrolytes; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D046911:Macromolecular Substances; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D011108:Polymers; D019814:Myristic Acid; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D000409:Alanine