Dynamics and Thermodynamics of Lipid — Protein Interactions in Membranes

Abstract

A thermodynamic analysis of the process of protein aggregation in membranes is presented. Three factors have been identified as the principal determinants of the state of aggregation or dispersal of the intrinsic proteins in simple membranes: The entropy of mixing, the equilibrium between boundary lipid and bilayer lipid, and protein-protein interactions. The Hamaker method was used to estimate the strength of the nonbonded dispersion energy between proteins embedded in lipid. It was found that this energy gives a net attractive force between the proteins and for large proteins may be several times the thermal energy, even when the proteins are separated by one or more lipid molecules. A limiting law equation for the athermal mixing of proteins and lipids in a membrane was derived using a lattice solution theory model. It is shown that the entropy of mixing varies inversely with the size of the proteins. Increasing the effective size of the proteins, as through dimerization by crosslinking agents, may induce a further nonspecific aggregation of proteins to occur, on account of the combined effect of an increased nonbonded attraction and a decreased entropy of mixing.