Translational diffusion coefficients of membrane protein aggregates in free and supported lipid membranes

TL;DR

This paper develops a theoretical model to accurately predict the translational diffusion coefficients of membrane protein aggregates by incorporating hydrodynamic interactions, with implications for understanding their biological functions.

Contribution

It introduces a hydrodynamic model for membrane protein aggregate diffusion, emphasizing the importance of hydrodynamic interactions and providing practical approximation methods.

Findings

Hydrodynamic interactions significantly increase diffusion coefficient estimates.

Derived hydrodynamic radii effectively characterize aggregate diffusivities.

Approximate methods allow diffusion estimation without resolving individual particles.

Abstract

There is increasing evidence that numerous membrane proteins can assemble into aggregates that modulate their function and affect many cellular processes such as signal transduction and endocytosis. Here, we present a theoretical description of the instantaneous translational diffusion coefficients of transmembrane protein aggregates on free and supported lipid membranes using Kirkwood-Riseman theory. We find that hydrodynamic interactions within protein aggregates must be accounted for, as neglecting them yields several times lower diffusion coefficients. By deriving hydrodynamic radii for free and supported lipid membranes, we identify effective length scales that accurately characterize aggregate diffusivities in the presence of hydrodynamic interactions. These findings motivate the approximation of an aggregate by its outline and a random particle distribution inside it. We show that this approach provides a practical method to accurately determine aggregate diffusion coefficients when the particle locations cannot be resolved. The results presented in this article have immediate implications for the formation and function of membrane protein aggregates.