Domain formation induced by the adsorption of charged proteins on mixed lipid membranes

Peripheral proteins can trigger the formation of domains in mixed. uid- like lipid membranes. We analyze the mechanism underlying this process for proteins that bind electrostatically onto a. at two- component membrane, composed of charged and neutral lipid species. Of particular interest are membranes in whichthe hydrocarbon lipid tails tend to segregate owing to nonideal chain mixing,but the ( protein- free) lipid membrane is nevertheless stable due to the electrostatic repulsion between the charged lipid headgroups. The adsorption of charged, say basic, proteins onto a membrane containing anionic lipids induces local lipid demixing, whereby charged lipids migrate toward ( or away from) the adsorption site, so as to minimize the electrostatic binding free energy. Apart from reducing lipid headgroup repulsion, this process creates a gradient in lipid composition around the adsorption zone, and hence a line energy whose magnitude depends on the protein's size and charge and the extent of lipid chain nonideality. Above a certain critical lipid nonideality, the line energy islarge enough to induce domain formation, i. e., protein aggregation and, concomitantly, macroscopic lipid phase separation. We quantitatively analyze the thermodynamic stability of the dressed membrane based on nonlinear Poisson- Boltzmann theory, accounting for both the microscopic characteristics of the proteins and lipid composition modulations at and around the adsorption zone. Spinodal surfaces and critical points of the dressed membranes are calculated for several different model proteins of spherical and disklike shapes. Among the models studied we. nd the most substantial protein- induced membrane destabilization for disk- like proteins whose charges are concentrated in the membrane- facing surface. If additional charges reside on the side faces of the proteins, direct protein- protein repulsion diminishes considerably the propensity fordomain formation. Generally, a highly charged. at face of a macroion appears most ef. cient in inducing large compositional gradients, hence a large and unfavorable line energy and consequently lateral macroion aggregation and, concomitantly, macroscopic lipid phase separation.