Anomalous diffusion and ergodicity in live cellsTracking an individual Kv2.1 channel labeled with a quantum dot.

The plasma membrane is a crowded environment where proteins and lipids move in the presence of mobile and immobile obstacles. Furthermore, membrane components often interact with cytosolic elements. We are exploring the dynamics of the voltage gated potassium channels Kv2.1and Kv1.4 and sodium channels Nav1.6, using single-molecule tracking. By dually labeling channels with GFP and quantum dots (QD), we gather information on both the individual molecule trajectories and the distribution of proteins in the plasma membrane as an ensemble.

 

Ergodicity breaking

We analyze Kv2.1 channel trajectories in terms of the time and ensemble distribution of square displacements. Our results reveal that Kv2.1 and Kv1.4 channels experience anomalous subdiffusion. We observe that the diffusion pattern is not ergodic, that is the ensemble and temporal distributions of displacements are different. The Kv2.1 channel dynamics can be accurately modeled by the combination of a nonergodic continuous time random walk (CTRW) and an obstructed environment.

 

Actin role on potassium channel dynamics

We are investigating the role of cortical actin in Kv2.1 channel dynamics by using actin inhibitors. Interestingly we see that upon application of actin inhibitors the Kv2.1 channel trajectories regain ergodicity, however still undergo anomalous diffusion. These results show that the actin cytoskeleton plays a dominant role in controlling the CTRW process.

 

Bulk-mediated diffusion

Diffusion at solid–liquid interfaces is crucial in many technological and biophysical processes. Although its behavior seems to be deceivingly simple, recent studies showing passive superdiffusive transport suggest that diffusion on surfaces may hide rich complexities. In particular, bulk-mediated diffusion occurs when molecules are transiently released from the surface to perform three-dimensional excursions into the liquid bulk. This phenomenon bears the dichotomy where a molecule always return to the surface but the mean jump length is infinite.

 

Publications

Weigel et al. "Ergodic and nonergodic processes coexist in the plasma membrane as observed by single molecule tracking", PNAS 108, 6438 (2011)

Weigel et al. “Obstructed diffusion propagator analysis for single particle tracking”, Phys. Rev. E 85, 041924 (2012)

Krapf, "Mechanisms underlying anomalous diffusion in the plasma membrane", Current Topics in Membranes 75, 167 (2015)

Campagnola et al., "Superdiffusive motion of membrane-targeting C2 domains", Sci. Rep. 5, 17721 (2015)

Krapf et al. "Strange kinetics of bulk-mediated diffusion on lipid bilayers", Phys. Chem. Chem. Phys. 18, 12633 (2016)

 

 

Group members involved

Sanaz Sadegh, Swarnava Pramanik, Kanti Nepal, Patrick Mannion

Collaborators

Mike Tamkun, Aleksander Weron, Krzysztof Burnecki, Olve Peersen

 

This project is supported by the National Science Foundation through grant 1401432.