Description:

Title: Anesthetics Act on a Membrane Critical Point

Speaker: Benjamin Machta, Princeton

Abstract: Many small molecules induce general anesthesia across animal species. Although their mechanism of action remains controversial, it is known that a compound's efficacy as an anesthetic is strongly predicted by both its hydrophobicity and its potency in inhibiting a wide variety of ligand-gated ion channels. I will argue that anesthetics influence ion channels through effects on their 2D solvent, the plasma membrane, which is tuned close to a liquid-liquid critical point. I will report on recent experiments where we show that the n-alcohol anesthetics take plasma membrane derived vesicles away from criticality by lowering their critical temperature (Tc), with 'intoxication reversers' acting opposite, actually raising Tc. I will then argue that criticality has profound consequences for membrane bound ion channels, leading to long range critical Casimir forces, sensitivity to compounds which alter Tc and seemingly non-Markovian dynamics, arising from information stored in critically slowed membrane composition modes. Our model predicts that activity should alter an ion channel’s surrounding lipid environment, a prediction we are beginning to test with super-resolution microscopy.

I will also give a brief overview of other areas of my ongoing research. I recently demonstrated that the energetic cost of controlling a thermodynamic system is bounded by the geodesic length of the control protocol, as defined by information geometry. I plan to use this and related finite time bounds to estimate the energetic cost of specific physical strategies for biological signal processing. I expect that strikingly different strategies like electrical depolarization, second messenger production and domain formation are each most energy efficient in particular spatial and temporal regimes.

Host: Adilson Motter

Keywords: Physics, Astronomy, Complex Systems