A computational model of cell membrane bioelectric polarization and depolarization, connected with cell proliferation, in different tissue geometries

Abstract

A reliable theory of biological tissues growth and organization, a fundamental tool for a comprehensive interpretation of experimental observations and a guide to progress in life sciences, is definitively missing. This would support the advancement of knowledge for both normal and pathological expansion and regulation of tissues and organisms. In this work is presented a computational model of cell culture that describes its growth and organization using cell proliferation as its default state, constrained by contact inhibition, closely connected to the cell bioelectric state. The model results describe in a correct way the reported experimental results, involving contact inhibition due to the presence of other cells, and gap junctions for signaling, molecules exchange and extracellular environment sensing. Starting from depolarized cells (in this model considered tantamount to proliferative), the cell culture grows until it fills the available domain and, due to the contact inhibition constraint, it turns into quiescence (a consequence of cell polarization), except on the periphery. Using drugs or via protein expression manipulation, it is possible to change the final tissue state, to fully polarized or depolarized. Other experimental tests are proposed and the expected results simulated. This model can be extended to pathological events, such as carcinogenesis, with cells homeostasis perturbed by a cell depolarizing (carcinogenic) event and express its default proliferative state without adequate control. This simplified model of tissue organization, regulated by the cell’s bioelectric state and their interaction with vicinity, is an alternative to the description of the experimental results by mechanical stress, and can be further tested and extended in dedicated experiments.