A thermodynamic framework for modelling membrane transporters

TL;DR

This paper introduces a physics-based, thermodynamically consistent modeling framework for membrane transporters, applied to cardiac SERCA and Na+/K+ ATPases, improving the realism of cellular transport models.

Contribution

It develops a thermodynamic modeling approach for membrane transporters, addressing inconsistencies in previous models and applying it to key cardiac transporters.

Findings

Models are thermodynamically consistent and physically realistic.

Application to cardiac transporters demonstrates improved accuracy.

Framework can be extended to other transporter systems.

Abstract

Membrane transporters contribute to the regulation of the internal environment of cells by translocating substrates across cell membranes. Like all physical systems, the behaviour of membrane transporters is constrained by the laws of thermodynamics. However, many mathematical models of transporters, especially those incorporated into whole-cell models, are not thermodynamically consistent, leading to unrealistic behaviour. In this paper we use a physics-based modelling framework, in which the transfer of energy is explicitly accounted for, to develop thermodynamically consistent models of transporters. We then apply this methodology to model two specific transporters: the cardiac sarcoplasmic/endoplasmic Ca$^{2+}$ ATPase (SERCA) and the cardiac Na$^+$/K$^+$ ATPase.