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Anisotropic environmental signals or polarized membrane ion/solute carriers can generate spatially varying intracellular gradients, leading to polarized cell dynamics. For example, the 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 physiology-relevant, physics-based mathematical model to reveal how ion carriers generate intracellular ion and voltage gradients. The model can 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, mechanical-biochemical coupling can modulate actin distribution and flow, creating a biphasic dependence of 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 highlights the importance of cell ion dynamics in modulating cell migration and cytoskeletal dynamics. Published by the American Physical Society2024
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This content will become publicly available on June 4, 2026
Generation of fate patterns via intercellular forces
Studies of fate patterning during development typically emphasize cell-cell communication via diffusible chemical signals. Recent experiments on stem cell colonies, however, suggest that in some cases mechanical stresses, rather than secreted chemicals, enable long-ranged cell-cell interactions that specify positional information and pattern cell fates. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony edge, more contractile than cells at the center, seed a pattern that propagates via force transmission. Strikingly, our model implies that the width of the outer fate domain varies nonmonotonically with substrate stiffness, a prediction that we confirm experimentally; we argue that a similar dependence on substrate stiffness can be achieved by a chemical morphogen only if strong constraints on the signaling pathway's mechanobiology are met. Our findings thus support the idea that mechanical stress can mediate patterning in the complete absence of chemical morphogens, even in nonmotile cell layers, thus expanding the repertoire of possible roles for mechanical signals in development and morphogenesis. Future tests of additional model predictions, like the effect of anisotropic substrate rigidity, will further broaden the range of achievable fate patterns. Published by the American Physical Society2025
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- Award ID(s):
- 2243624
- PAR ID:
- 10599422
- Publisher / Repository:
- American Physical Society
- Date Published:
- Journal Name:
- Physical Review Research
- Volume:
- 7
- Issue:
- 2
- ISSN:
- 2643-1564
- Page Range / eLocation ID:
- L022051
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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