Physical limits on galvanotaxis

TL;DR

This paper models how cells sense electric fields during galvanotaxis, revealing physical limits imposed by molecular noise and proposing a universal curve for directional response based on sensor redistribution.

Contribution

It introduces a quantitative model linking sensor redistribution to galvanotactic behavior, predicting universal response curves and sensor property constraints.

Findings

Galvanotactic directionality follows a universal curve across cell types.

Cells can achieve observed directionalities with few highly polarized sensors or many less polarized sensors.

Sensor redistribution signatures suggest a tradeoff between accuracy and variance in response to changing fields.

Abstract

Eukaryotic cells can polarize and migrate in response to electric fields via "galvanotaxis," which aids wound healing. Experimental evidence suggests cells sense electric fields via molecules on the cell's surface redistributing via electrophoresis and electroosmosis, though the sensing species has not yet been conclusively identified. We develop a model that links sensor redistribution and galvanotaxis using maximum likelihood estimation. Our model predicts a single universal curve for how galvanotactic directionality depends on field strength. We can collapse measurements of galvanotaxis in keratocytes, neural crest cells, and granulocytes to this curve, suggesting that stochasticity due to the finite number of sensors may limit galvanotactic accuracy. We find cells can achieve experimentally observed directionalities with either a few (~100) highly-polarized sensors, or many (~10,000) sensors with a ~6-10% change in concentration across the cell. We also identify additional signatures of galvanotaxis via sensor redistribution, including the presence of a tradeoff between accuracy and variance in cells being controlled by rapidly switching fields. Our approach shows how the physics of noise at the molecular scale can limit cell-scale galvanotaxis, providing important constraints on sensor properties, and allowing for new tests to determine the specific molecules underlying galvanotaxis.