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Title: Cell migration dynamics explained by the coupling of mechanics with electrochemistry and pH regulation

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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Award ID(s):
2303648
NSF-PAR ID:
10527438
Author(s) / Creator(s):
;
Publisher / Repository:
American Physical Society
Date Published:
Journal Name:
Physical Review Research
Volume:
6
Issue:
2
ISSN:
2643-1564
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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Retrieved from https://par.nsf.gov/biblio/10527438. <em>Physical Review Research</em> 6.2 Web. doi:10.1103/PhysRevResearch.6.023158. </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-apa" data-toggle="modal">APA</a> <div id="cite-apa" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-apa_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-apa_label">Cite: APA Format</strong> </div> <div class="modal-body">Li, Yizeng, & Sun, Sean X. <em>Cell migration dynamics explained by the coupling of mechanics with electrochemistry and pH regulation</em>. <em>Physical Review Research</em>, <em>6</em> (2). Retrieved from https://par.nsf.gov/biblio/10527438. <a href="https://doi.org/10.1103/PhysRevResearch.6.023158">https://doi.org/10.1103/PhysRevResearch.6.023158</a> </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-chi" data-toggle="modal">Chicago</a> <div id="cite-chi" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-chi_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-chi_label">Cite: Chicago Format</strong> </div> <div class="modal-body">Li, Yizeng, and Sun, Sean X. "Cell migration dynamics explained by the coupling of mechanics with electrochemistry and pH regulation". <em>Physical Review Research</em> 6 (2). Country unknown/Code not available: American Physical Society. <a href="https://doi.org/10.1103/PhysRevResearch.6.023158">https://doi.org/10.1103/PhysRevResearch.6.023158.</a> <a href="https://par.nsf.gov/biblio/10527438">https://par.nsf.gov/biblio/10527438</a>. </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-bib" data-toggle="modal">BibTeX</a> <div id="cite-bib" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-bib_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-bib_label">Cite: BibTeX Format</strong> </div> <div class="modal-body"> @article{osti_10527438,<br/> place = {Country unknown/Code not available}, title = {Cell migration dynamics explained by the coupling of mechanics with electrochemistry and pH regulation}, url = {https://par.nsf.gov/biblio/10527438}, DOI = {10.1103/PhysRevResearch.6.023158}, abstractNote = {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}, journal = {Physical Review Research}, volume = {6}, number = {2}, publisher = {American Physical Society}, author = {Li, Yizeng and Sun, Sean X}, }</div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="divider"></li> </ul> <ul class="nav nav-list" style="font-size: 14px; font-family: Arial Regular;"> <li class="nav-header header-format">Export Metadata</li> <li class="links-format"><a href="https://par.nsf.gov/endnote?osti_id=10527438">EndNote</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:excel/osti-id:10527438">Excel</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:csv/osti-id:10527438">CSV</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:xml/osti-id:10527438">XML</a></li> <li class="divider"></li> </ul> <ul class="nav nav-list" style="font-size: 14px; 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