Unexpected complexities of macromolecular diffusion in membranes and dense protein solutions
Max-Planck-Institut für Biophysik, Frankfurt, Germany
We studied the diffusion of proteins and other macromolecules in dense and dilute solution, and in lipid membranes using molecular dynamics simulations. In systems mimicking the interior of a living cell, with densely packed proteins, translational and rotational diffusion of proteins slow down dramatically at high protein concentrations, and the Stokes-Einstein relation appears to break down. Transient clustering of proteins is the underlying cause, explaining both the resulting increase in the apparent Stokes radius and the rise in the viscosity within the theoretical framework of attractive colloidal systems.
Overall, long simulation trajectories of large membrane, protein, and nucleic acid systems give us a remarkably rich picture of macromolecular diffusion. In concentrated systems, diffusion is hindered dramatically even by weak and transient interactions; in membranes, diffusion appears to break down entirely. However, hydrodynamic theory resolves these challenges and corrects for the system-size dependences, giving us diffusion coefficients that can be interpreted meaningfully and compared to experiment.
About the speaker: Gerhard Hummer is Director of the MPI for Biophysics in Frankfurt, where he leads the Department of Theoretical Biophysics. He uses molecular simulations, modeling, and theory to study the structure and dynamics of biological systems at the molecular level, in order to elucidate their function. His current research focuses on molecular principles in bioenergetics, membrane transport, and membrane remodeling. Prof. Hummer is Fellow of the APS and has received, among other prizes, the Raymond and Beverly Sackler International Prize in Biophysics.