Pre-transition effects mediate forces of assembly between transmembrane proteins

TL;DR

This paper introduces the orderphobic effect, a pre-transition force in lipid bilayers that promotes transmembrane protein assembly by stabilizing order-disorder interfaces near phase transitions, with implications for membrane dynamics.

Contribution

It reveals a novel pre-transition mechanism for protein assembly in membranes, mediated by order-disorder interfaces, expanding understanding of membrane-protein interactions.

Findings

Orderphobic effect is stronger than elastic membrane forces.

Proteins stabilize microscopic interfaces near phase transition.

Assembly driven by reduction in interfacial free energy.

Abstract

We present a mechanism for a generic and powerful force of assembly and mobility for transmembrane proteins in lipid bilayers. This force is a pre-transition (or pre-melting) effect for the first-order transition between ordered and disordered phases in the host membrane. Using large scale molecular simulation, we show that a protein with hydrophobic thickness equal to that of the disordered phase embedded in an ordered bilayer stabilizes a microscopic order-disorder interface, and the stiffness of that interface is finite. When two such proteins approach each other, they assemble because assembly reduces the net interfacial free energy. In analogy with the hydrophobic effect, we refer to this phenomenon as the "orderphobic effect". The effect is mediated by proximity to the order-disorder phase transition and the size and hydrophobic mismatch of the protein. The strength and range of forces arising from the orderphobic effect are significantly larger than those that could arise from membrane elasticity for the membranes we examine.