# Universal kinetics for engagement of mechanosensing pathways in cell adhesion

## TL;DR

This study reveals universal kinetic behaviors in cell adhesion mechanosensing pathways, showing that population spreading dynamics are governed by thermal activation over a single energy barrier, independent of substrate stiffness.

## Contribution

It uncovers a universal kinetic model for cell spreading that is driven by thermal activation and involves a five-component adhesion complex, advancing understanding of mechanosensing.

## Key findings

- Population dynamics are substrate stiffness independent.
- Long-time statistics follow thermal activation over 19 kcal/mol barrier.
- Early-time kinetics follow a power law t^5.

## Abstract

When plated onto substrates, cell morphology and even stem cell differentiation are influenced by the stiffness of their environment. Stiffer substrates give strongly spread (eventually polarized) cells with strong focal adhesions, and stress fibers; very soft substrates give a less developed cytoskeleton, and much lower cell spreading. The kinetics of this process of cell spreading is studied extensively, and important universal relationships are established on how the cell area grows with time. Here we study the population dynamics of spreading cells, investigating the characteristic processes involved in cell response to the substrate. We show that unlike the individual cell morphology, this population dynamics does not depend on the substrate stiffness. Instead, a strong activation temperature dependence is observed. Different cell lines on different substrates all have long-time statistics controlled by the thermal activation over a single energy barrier dG=19 kcal/mol, while the early-time kinetics follows a power law $t^5$. This implies that the rate of spreading depends on an internal process of adhesion-mechanosensing complex assembly and activation: the operational complex must have 5 component proteins, and the last process in the sequence (which we believe is the activation of focal adhesion kinase) is controlled by the binding energy dG.