The influence of polarized membrane ion carriers and extracellular electrical/pH gradients on cell ionic homeostasis and locomotion

Abstract

AbstractAnisotropic environmental signals or polarized membrane ion/solute carriers can generate spatially-varying intracellular gradients, leading to polarized cell dynamics. For example, directional migration of neutrophils, galvanotaxis of glioblastoma, and water flux in kidney cells, all result from the polarized distribution of membrane ion carriers and other intracellular components. The underlying physical mechanisms behind how polarized ion carriers interact with environmental signals are not well studied. Here, we use a physiologically-relevant, physics-based mathematical model to reveal how ion carriers generate intracellular ionic and voltage gradients. The model is able to discern the contribution of individual ion carriers to the intracellular pH gradient, electric potential, and water flux. We discover that an extracellular pH gradient leads to an intracellular pH gradient via chloride-bicarbonate exchangers, whereas an extracellular electric field leads to an intracellular electric potential gradient via passive potassium channels. In addition, the mechanical-biochemical coupling can modulate actin distribution and flow, and create biphasic dependence of the cell speed on water flux. Moreover, we find that F-actin interaction with NHE alone can generate cell movement, even when other ion carriers are not polarized. Taken together, the model shows the importance of cell ion dynamics in modulating cell migration and cytoskeletal dynamics.