The living state: How cellular excitability is controlled by the thermodynamic state of the membrane

The thermodynamic (TD) properties of biological membranes play a central role for living systems. It has been suggested, for instance, that nonlinear pulses such as action potentials (APs) can only exist if the membrane state is in vicinity of a TD transition. Herein, two membrane properties in living systems - excitability and velocity - are analyzed for a broad spectrum of conditions (temperature (T), 3D-pressure (p) and pH-dependence). Based on experimental data from Characean cells and a review of literature we predict parameter ranges in which a transition of the membrane is located (15 -35 degrees C below growth temperature; 1 - 3 pH units below pH 7; at similar to 800 atm) and propose the corresponding phase diagrams. The latter explain: (i) changes of AP velocity with T; p and pH:(ii) The existence and origin of two qualitatively different forms of loss of nonlinear excitability (nerve block, anesthesia). (iii) The type and quantity of parameter changes that trigger APs. Finally, a quantitative comparison between the TD behavior of 2D-lipid model membranes with living systems is attempted. The typical shifts in transition temperature with pH and p of model membranes agree with values obtained from cell physiological measurements. Taken together, these results suggest that it is not specific molecules that control the excitability of living systems but rather the TD properties of the membrane interface. The approach as proposed herein can be extended to other quantities (membrane potential, calcium concentration, etc.) and makes falsifiable predictions, for example, that a transition exists within the specified parameter ranges in excitable cells. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

The thermodynamic properties of biological membranes, particularly regarding temperature, pressure, and pH, play a central role in the excitability and velocity of living systems. Experimental data and literature review predict parameter ranges for membrane transitions, explaining changes in action potential velocity, loss of excitability, and triggers for action potentials. This study suggests that the thermodynamic properties of membrane interfaces, rather than specific molecules, control excitability in living systems.