Autologous chemotaxis at high cell density

TL;DR

This paper models autologous chemotaxis at high cell densities, revealing conditions under which sensing fails or reverses, and relates these findings to cancer cell behavior in dense tumor environments.

Contribution

It introduces a minimal model predicting the cell density threshold for sensing failure and explains the reversal of chemotaxis in oversaturated environments.

Findings

Sensing fails at a specific cell density predicted by the model

Chemotaxis can reverse direction in oversaturated conditions

Model aligns with experimental observations of metastatic cancer cells

Abstract

Autologous chemotaxis, in which cells secrete and detect molecules to determine the direction of fluid flow, is thwarted at high cell density because molecules from other cells interfere with a given cell's signal. Using a minimal model of autologous chemotaxis, we determine the cell density at which sensing fails and find that it agrees with experimental observations of metastatic cancer cells. To understand this agreement, we derive a physical limit to autologous chemotaxis in terms of the cell density, the P\'eclet number, and the length scales of the cell and its environment. Surprisingly, in an environment that is uniformly oversaturated in the signaling molecule, we find that sensing not only can fail, but can be reversed, causing backwards cell motion. Our results get to the heart of the competition between chemical and mechanical cellular sensing and shed light on a sensory strategy employed by cancer cells in dense tumor environments.