Superdiffusive motion of membrane-targeting C2 domains

TL;DR

This study investigates the superdiffusive behavior of membrane-targeting C2 domains, revealing that bulk excursions cause large jumps that enhance membrane exploration, with implications for membrane-associated reactions.

Contribution

It demonstrates that bulk-mediated jumps cause superdiffusion in membrane proteins, combining experimental single-molecule tracking with analytical models and simulations.

Findings

Ensemble-averaged MSD shows superdiffusion.

Individual trajectories appear linear in time-averaged MSD.

Bulk excursions cause large, heavy-tailed jumps.

Abstract

Membrane targeting domains play crucial roles in the association of signalling molecules to the plasma membrane. For most peripheral proteins, the protein-to-membrane interaction is transient. After proteins dissociate from the membrane they have been observed to rebind following brief excursions in the bulk solution. Such membrane hops can have broad implications for the efficiency of reactions on membranes. We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behaviour. However, traditional time-averaged MSD analysis of individual trajectories remains linear and it does not reveal superdiffusion. Our observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. These hopping events allow proteins to explore large areas in a short time. The experimental results are shown to be consistent with analytical models of bulk-mediated diffusion and numerical simulations.