Cells actively exert forces to their surrounding environment — an interconnected fibrous network in which they are embedded, known as the extracellular matrix (ECM). The ECM demonstrates a unique mechanical behavior, showing a highly non-linear response to tensile and compressive forces alike.

Forces generated by cells can travel hundreds of microns away through the matrix to reach distant cells. These far-traveling forces are thus considered as a means for cells to mechanically “communicate” with each other. This mechanism has been shown to mediate various biological processes as diverse as capillary sprouting, cancer invasion, heart-beat synchronization, and cell morphogenesis.

Long-distance mechanical interactions between neighboring cells are associated with intense remodeling of the fibrous matrix, manifested by aligned and densely packed fiber “bands” forming between the cells. The cover image presented on the October 2 issue of Biophysical Journal shows an example of two green fluorescent protein-actin fibroblast cells embedded in a fluorescently labeled fibrin gel (confocal microscopy image). The cells deform their surrounding fibrous environment in a highly directional manner toward each other, creating directed matrix “bands” between them.

But how do these “bands” form in such a directed manner between the cells? Does this process relate to the unique mechanical properties of the matrix in which the cells are embedded? With the aim of exploring these questions we developed a finite element model that allowed us to examine the influence of the nonlinear mechanical behavior of the ECM, the level of cell contractility and the distance between neighboring cells — each factor independently — on the transmission of loads between the cells. Our findings reveal the contribution of the nonlinear mechanical properties of the ECM to the efficient transmission of mechanical signals between cells.

- Ran Sopher, Hanan Tokash, Sari Natan, Mirit Sharabi, Ortal Shelah, Oren Tchaicheeyan, Ayelet Lesman