Surface forces in the aggregation of membrane proteins

Abstract

The membranes of living cells have specialized protein assemblies called channels that control ion transport. The structural similarities between different channels suggest a common design and mode of operation. We are studying the effect of surface charge on protein aggregation/disaggregation reactions as the basis for channel function and the link to electrical stimuli. Since aggregation/disaggregation reactions appear to involve changes at the interfaces of the subunits rather than in the internal structure, we have assumed that the total free energy change in such reactions can be evaluated in terms of the surface free energy change. This assumption leads to the correct prediction of the variation of the disaggregation constant with pH, as well as the variation of hemoglobin viscosity with concentration and the variation of the oxygenation equilibrium with pH and ionic strength. The model also leads to a simple explanation of the Hill coefficient of cooperative reactions in terms of a Gibbs surface excess. The application of the surface free energy model to the voltage gated channels of excitable membranes leads to an understanding of their opening/closing reactions and their apparent selectivity. The calculated ion fluxes using the surface compartment model equations are similar to those observed in the sodium and potassium channels of excitable membranes.