  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.
