# Mechanical Interaction Between Cells Facilitates Molecular Transport

## TL;DR

This study reveals how mechanical forces exerted by cells on the extracellular matrix can enhance molecular transport by restructuring fibers, transforming diffusion pathways from 3D to 1D and facilitating long-range cell communication.

## Contribution

It introduces a computational model demonstrating that cell-induced ECM remodeling accelerates molecular transport by fiber alignment and densification, revealing a mechano-biochemical feedback mechanism.

## Key findings

- ECM remodeling increases fiber alignment and density over time.
- Transport speed of molecules between cells is significantly increased.
- Transport pathway dimensionality reduces from 3D to 1D due to fiber alignment.

## Abstract

In vivo, eukaryotic cells are embedded in a matrix environment, where they grow and develop. Generally, this extracellular matrix (ECM) is an anisotropic fibrous structure, through which macromolecules and biochemical signaling molecules at the nanometer scale diffuse. The ECM is continuously remodeled by cells, via mechanical interactions, which lead to a potential link between biomechanical and biochemical cell-cell interactions. Here, we study how cell-induced forces applied on the ECM impacts the biochemical transport of molecules between distant cells. Experimentally, we observe that cells remodel the ECM by increasing fiber alignment and density of the matrix between them over time. Using random walk simulations on a 3D lattice, we implement elongated fixed obstacles that mimic the fibrous ECM structure. We measure both diffusion of a tracer molecule and the mean first-passage time a molecule secreted from one cell takes to reach another cell. Our model predicts that cell-induced remodeling can lead to a dramatic speedup in the transport of molecules between cells. Fiber alignment and densification cause reduction of the transport dimensionality from a 3D to a much more rapid 1D process. Thus, we suggest a novel mechanism of mechano-biochemical feedback in the regulation of long-range cell-cell communication.