MOLECULAR MECHANISM OF PROTEIN INTERACTIONS WITH THE LIPID BILAYER-MEMBRANE

Interactions between various solvated particles (including ions, proteins, and lipid vesicles) and a membrane surface are discussed from the experimental and theoretical point of view. It is shown that, irrespective of particle size, the short range forces always involve electrostatic and/or van der Waals attraction; in the thermodynamic equilibrium, these forces are balanced by a steric, solvent-modified repulsion which is mainly a function of the surface hydrophilicity. Dynamical phenomena, including lateral density fluctuations, defect formation, and out-of-plane fluctuations, also play a role. The dynamic effects are relatively more important for the large-size macromolecules or supramolecules. Non-specific adsorption of proteins, such as serum albumin, to a lipid membrane is governed by the steep membrane-repulsion barrier and, even more importantly, by the number of the 'hydrophobic binding sites' at the membrane surface. The amount of adsorbed protein, consequently, is proportional to the density of the membrane defects and often has a peak in the vicinity of the lipid chain-melting phase transition. Normally, the non-specific adsorption of proteins begins instantaneously after addition but may take many hours, or days, to reach completion. Specific binding of a protein, such as antibody, to the haptenated or receptor-carrying membranes is chiefly sensitive to the net dynamic hydration force at or near the membrane surface. Strong hydrational repulsion, which has a range on the order of 3 nm for pure lipid bilayers, typically diminishes the efficiency of the antibody-surface association as compared to the binding in bulk. For uncharged lipid bilayer membranes the probability for protein adsorption or binding decreases with the increasing surface polarity (hydrophilicity).