Mechanical Interaction between Cells Facilitates Molecular Transport

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, it is studied how cell-induced forces applied on the ECM impact the biochemical transport of molecules between distant cells. It is experimentally observed 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, elongated fixed obstacles are implemented that mimic the fibrous ECM structure. Both diffusion of a tracer molecule and the mean first-passage time a molecule secreted from one cell takes to reach another cell are measured. The 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, a novel mechanism of mechano-biochemical feedback in the regulation of long-range cell-cell communication is suggested.

Keywords: cell-cell communication; fibrous extracellular matrix; mean first passage time; molecular transport; transport through porous media.