Back

Anomalous diffusion and ergodicity in live cells

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.

Tracking an individual Kv2.1 channel labeled with a quantum dot.

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.

Kv2.1 voltage gated potassium channels

Kv2.1 are potassium channels that play an important physiological role in numerous cell types and tissues. In particular, in the mammalian neurons, these channels have a protective function in response to stroke suppressing seizures which aggravate brain damage. This critical role is achieved by forming and regulating Kv2.1 surface clusters. Nevertheless, up to date, the physical mechanism behind the cluster maintenance is largely unknown. We aim at revealing the mechanism of Kv2.1 channel cluster formation using optical tweezers assays and high-speed particle tracking with nanometer resolution in live mammalian cells. A greater understanding of how this channel is dynamically localized may lead to improved treatments for stroke, the third leading cause of death in the United States and a major cause of long term disability. We aim at unraveling the mechanisms underlying membrane dynamics, surface protein localization and channel surface formation in order to improve our knowledge of these molecular processes and advance human health.

Publications:

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

Group members involed

Aubrey Weigel
Kari Ecklund
Mike Reid

Collaborators

Mike Tamkun, Liz Akin.