Bilayer-thickness-mediated interactions between integral membrane proteins

Abstract

Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayer-mediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression and expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions. Here we develop a combined analytic and numerical methodology for the solution of the equilibrium elastic equations associated with protein-induced lipid bilayer deformations. Our methodology allows accurate prediction of thickness-mediated protein interactions for arbitrary protein symmetries at arbitrary protein separations and relative orientations. We provide exact analytic solutions for cylindrical integral membrane proteins with constant and varying hydrophobic thickness, and develop perturbative analytic solutions for non-cylindrical protein shapes. We complement these analytic solutions, and assess their accuracy, by developing both finite element and finite difference numerical solution schemes. Taken together, the work presented here puts into place an analytic and numerical framework which allows calculation of bilayer-mediated elastic interactions between integral membrane proteins for the complicated protein shapes suggested by structural biology and at the small protein separations most relevant for the crowded membrane environments provided by living cells.

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Cited by in corpus (6)

• Elastic multipole method for describing linear deformation of infinite 2D solid structures with circular holes and inclusions
• Method of image charges for describing linear deformation of bounded 2D solid structures with circular holes and inclusions
• Controlling the shape of membrane protein polyhedra
• Dependence of protein-induced lipid bilayer deformations on protein shape
• Thermodynamic competition between membrane protein oligomeric states
• Coupling of Lipid Phase Behavior and Protein Oligomerization in a Lattice Model of Raft Membranes