Insertion and pore formation driven by adsorption of proteins onto lipid bilayer membrane-water interfaces

We describe the binding of proteins to lipid bilayers in the case for which binding can occur either by adsorption to the lipid bilayer membrane-water interface or by direct insertion into the bilayer itself. We examine in pa rticular the case when the insertion and pore formation are driven by the a dsorption process using scaled particle theory. The adsorbed proteins form a two-dimensional "surface gas" at the lipid bilayer membrane-water interfa ce that exerts a lateral pressure on the lipid bilayer membrane. Under cond itions of strong intrinsic binding and a high degree of interfacial converg e, this pressure can become high enough to overcome the energy barrier for protein insertion. Under these conditions, a subtle equilibrium exists betw een the adsorbed and inserted proteins. We propose that this provides a con trol mechanism for reversible insertion and pore formation of proteins such as melittin and magainin. Next, we discuss experimental data for the bindi ng isotherms of cytochrome c to charged lipid membranes in the light of our theory and predict that cytochrome c inserts into charged lipid bilayers a t low ionic strength. This prediction is supported by titration calorimetry results that are reported here. We were furthermore able to describe the o bserved binding isotherms of the pore-forming peptides endotoxin (alpha5-he lix) and of pardaxin to zwitterionic vesicles from our theory by assuming a dsorption/insertion equilibrium.