Physical limits on galvanotaxis via transmembrane protein electrophoresis is dependent on cell morphology and orientation

Eukaryotic cells respond to electric fields during wound healing and embryogenesis, a process known as galvanotaxis. This behavior is intricately linked to cell morphology, orientation, and the redistribution of transmembrane proteins through electrophoresis. We recently developed a theoretical model that establishes a connection between the redistribution of proteins and galvanotaxis using maximum likelihood estimation. Our model suggests that limitations of galvanotactic responses may stem from stochasticity due to the finite number of proteins. The model also accounts for cell shape and orientation, revealing that cells possess more information about the electric field direction along their long axis. However, they also experience greater variation in their estimation of the field direction along this axis. Our model predicts that if cells estimate the field direction by taking the average of all the protein locations, this introduces a bias towards the short axis. The amount of information, difference in estimate variance between axes, and bias towards the short axis increase as a cell gets larger and more eccentric. We also established a link between the redistribution of proteins and cell shape, demonstrating that cells can expand with their long axis perpendicular to the electric field for experimentally valid parameters, a phenomenon commonly observed by cells such as keratocytes and fibroblasts. IN acknowledges funding from NIH Grant Program in Molecular Biophysics 5T32GM135131.