Electromechanics and Volume Dynamics in Nonexcitable Tissue Cells

Abstract

Cell volume regulation is fundamentally important in phenomena such as cell growth, proliferation, tissue homeostasis, and embryogenesis. How the cell size is set, maintained, and changed over a cell's lifetime is not well understood. In this work we focus on how the volume of nonexcitable tissue cells is coupled to the cell membrane electrical potential and the concentrations of membrane-permeable ions in the cell environment. Specifically, we demonstrate that a sudden cell depolarization using the whole-cell patch clamp results in a 50% increase in cell volume, whereas hyperpolarization results in a slight volume decrease. We find that cell volume can be partially controlled by changing the chloride or the sodium/potassium concentrations in the extracellular environment while maintaining a constant external osmotic pressure. Depletion of external chloride leads to a volume decrease in suspended HN31 cells. Introducing cells to a high-potassium solution causes volume increase up to 50%. Cell volume is also influenced by cortical tension: actin depolymerization leads to cell volume increase. We present an electrophysiology model of water dynamics driven by changes in membrane potential and the concentrations of permeable ions in the cells surrounding. The model quantitatively predicts that the cell volume is directly proportional to the intracellular protein content.

Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation

“…Therefore, the total intracellular solute concentration remains almost constant regardless of the cell volume. This is consistent with our previous results on cell volume variations as a function of membrane potential (Yellin et al, 2018 ). In this work, we have focused on a spherical cell.…”

“…Given the large overall osmolarity of the intracellular and extracellular environments, which is on the order of 100 mM, the Δ c is negligible and is often approximated as zero (Mori, 2012 ). Equation 29 can further be simplified as The leading order solution is On the leading order, the cell volume is Equation 32 shows that the cell volume is linear in N HBuf + N Buf and N A due to the assumed impermeability of the buffer solution and proteins in the model (Kay, 2017 ; Yellin et al, 2018 ). Different cells may have different amounts and types of buffer solutions and proteins.…”

“…The overall permeability scale, α 0 , is chosen such that the predicted transient response upon perturbation lasts about 10 min before the system reaches a steady state. This time scale comes from both our experimental observation when cells typically research steady-state after perturbation (Yellin et al, 2018 ) and the possible magnitude of fluxes from the average number of ion channels, transporters, or pumps per unit cell surface area (Gadsby, 2009 ). The relative permeability coefficients of various ion channels, transporters, and pumps, such as α NKE /α 0 , α NKCC /α 0 , α NHE /α 0 , and α AE2 /α 0 , are fitted such that the model output vector, , is consistent with physiological-relevant numbers reported in the literature.…”

Regulation of Cell Behavior by Hydrostatic Pressure

“…Florence et al [136] systematically investigated Na þ , K þ , and Clions and transmembrane electrical potential in cell volume regulation. By controlling the electrical potential through a wholecell patch clamp experiment, they find that cell volume increases with depolarization.…”

Detection of the mesenchymal-to-epithelial transition of invasive non-small cell lung cancer cells by their membrane undulation spectra

“…38,39 This suggests that the observed surface undulation of tumor cells may be caused by associated cytoskeleton and adhesion dynamics inside. [40][41][42] On the other hand, recent evidence has also demonstrated that slow changes in the cellular volume can be triggered by active cross-membrane transport of water and ion molecules, 19,[43][44][45][46] which could also lead to the surface undulation of cells. Further investigations are certainly Fig.…”