Statistical thermodynamics of membrane bending mediated protein-protein attraction

Integral membrane proteins deform the surrounding bilayer creating long-ranged forces that influence distant proteins. These forces can be attractive or repulsive, depending on the proteins’ shape, height, contact angle with the bilayer, as well as the local membrane curvature. Although interaction energies are not pairwise additive, for sufficiently low protein density, thermodynamic properties depend only upon pair interactions. Here, we compute pair interaction potentials and entropic contributions to the two-dimensional osmotic pressure of a collection of noncircular proteins. In contrast to direct short-ranged interactions such as van der Waal’s, hydrophobic, or electrostatic interactions, both local membrane Gaussian curvature and protein ellipticity can induce attractions between two proteins at distances of up to ten times their typical radii. For flat membranes, bending rigidities of ∼ 30kBT , and moderate ellipticities, we find thermally averaged attractive interactions of order ∼ 2kBT . These interactions may play an important role in the intermediate stages of protein aggregation.