The combined hydrodynamic and thermodynamic effects of immobilized proteins on the diffusion of mobile transmembrane proteins

Abstract

The plasma membranes of cells are thin viscous sheets in which some transmembrane proteins have two-dimensional mobility and some are immobilized. Previous studies have shown that immobile proteins retard the short-time diffusivity of mobile particles through hydrodynamic interactions and that steric effects of immobile proteins reduce the long-time diffusivity in a model that neglects hydrodynamic interactions. We present a rigorous derivation of the long-time diffusivity of a single mobile protein interacting hydrodynamically and thermodynamically with an array of immobile proteins subject to periodic boundary conditions. This method is based on a finite element method (FEM) solution of the probability density of the mobile protein diffusing with a position-dependent mobility determined through a multipole solution of Stokes equations. The simulated long-time diffusivity in square arrays decreases as the spacing in the array approaches the particle size in a manner consistent with a lubrication analysis. In random arrays, steric effects lead to a percolation threshold volume fraction above which long-time diffusion is arrested. The FEM/multipole approach is used to compute the long-time diffusivity far away from this threshold. An approximate analysis of mobile protein diffusion through a network of pores connected by bonds with resistances determined by the FEM/multipole calculations is then used to explore higher immobile area fractions and to evaluate the finite simulation cell size scaling behaviour of diffusion near the percolation threshold. Surprisingly, the ratio of the long-time diffusivity to the spatially averaged short-time diffusivity in these two-dimensional fixed arrays is higher in the presence of hydrodynamic interactions than in their absence. Finally, the implications of this work are discussed, including the possibility of using the methods developed here to investigate more complex diffusive phenomena observed in cell membranes.