A Model for Anesthetic Effects on Cell Membranes

Ion channels in the plasma membrane are the functional units of neurons and their misregulation by anesthetic compounds is thought to be the proximate cause of the organism-level anesthetic response. However, the mechanism through which general anesthetics affect these channels remains an open question: although many drugs function by binding to receptors in the cell membrane, the variability in compounds that act as anesthetics suggests that they may have a different mode of operation. Recent experiments have shown that anesthetics lower the transition temperature, TC , of a liquid-liquid miscibility critical point of Giant Plasma Membrane-derived Vesicles (GPMVs), and further that the magnitude of this effect is well correlated with the potency of the anesthetic. To understand how anesthetics affect TC , we developed a simple Ising model for the membrane as a 2D binary liquid. In our model, Ising spins represent membrane lipids; annealed vacancies, which solubilize the two liquid phases, represent anesthetic molecules. We provide theoretical predictions for 1) the change in Tc of the membrane as a function of the potency-normalized amount of anesthetic in a volume surrounding it and 2) the mole fraction of anesthetic in the membrane at anesthetic dose. We demonstrate that these predictions are in good agreement with results from GPMV assays and synthetic bilayers, respectively. Ofer Kimchi ’16 Department of Physics Program in Applied and Computational Mathematics Princeton University Advisor: Benjamin Machta Second Reader: William Bialek This paper represents my own work in accordance with University regulations.