Karthik Shekhar, Assistant Professor, Dept. of Chemical and Biomolecular Engineering, University of California, Berkeley

"The multiscale dynamics of bioelectricity"

Abstract:

Bioelectricity—the ability of living cells to generate and use electrical signals—underlies sensation, movement, thought, and memory. The pioneering work of Hodgkin and Huxley, recognized by the 1963 Nobel Prize in Physiology and Medicine, revealed the ionic basis of membrane excitability and foreshadowed the discovery of ion channels. Yet their circuit framework necessarily averaged over localized nanoscale currents and the physical structure of membranes. We seek a multiscale theory connecting these microscopic processes to cellular electrical behavior towards understanding natural excitability, discovering new electrical states, and designing controllable bioelectric systems.

In the first part, I will show how the electrochemical response of a biological membrane to the activity of a single ion channel is shaped by diffuse-charge dynamics and membrane geometry, producing a hierarchy of spatiotemporal transport regimes. I will then show how classical circuit descriptions, including cable theory, systematically emerge from this underlying physics—and where their simplifying assumptions conceal important behavior.

In the second part, I will ask whether dense channel assemblies constitute a missing level of organization between single-molecule kinetics and whole-cell excitability. We show that voltage-gated channels can undergo nonequilibrium bioelectrical phase transitions, collectively switching between predominantly closed and open states while generating propagating electrical fronts, critical scaling, and abrupt changes in activity. These collective phenomena may be particularly relevant to specialized axonal structures in living nervous systems.