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

## TL;DR

This paper investigates how the thermodynamic properties of biological membranes influence cellular excitability and action potential propagation, revealing phase transitions that explain various physiological phenomena.

## Contribution

It predicts membrane phase transition ranges under different conditions and links thermodynamic states to excitability, providing a unifying framework for understanding nerve function.

## Key findings

- Membrane excitability is governed by thermodynamic phase transitions.
- Action potential velocity varies with temperature, pH, and pressure.
- Loss of excitability can be explained by membrane phase behavior.

## Abstract

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 - excitability and AP velocity - are investigated for a broad spectrum of conditions in living systems (temperature (T), 3D-pressure (p) and pH dependence). Based on these data we predict parameter ranges in which a transition of the membrane is located (15-35{\deg}C below growth temperature; 1-3 pH units below pH 7; at ~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 blockage", anesthesia). (iii) The type and quantity of parameter changes that trigger APs. Finally, a quantitative comparison between the TD behaviour of 2D-lipid model membranes with living systems is attempted. The typical shifts in transition temperature with pH and p of model membranes agree closely with values obtained from cell physiological measurements (excitability and propagation velocity). Taken together, these results strongly suggest that it is not specific molecules that control the excitability of living systems but rather the TD properties of the quasi 2D-membrane interface. The approach as proposed herein can be extended to other quantities (surface potential, calcium concentration, etc.) and makes clearly falsifiable predictions, for example, that a transition exists within the specified parameter ranges in excitable cells.

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Source: https://tomesphere.com/paper/1905.06541