Quantifying the dynamics of long-range cell-cell mechanical communication

Cells sense, manipulate and respond to the mechanical properties of their microenvironment in a plethora of physiological processes, yet whether and how cells interpret environmental cues to communicate with distant cells is mostly unknown. We present a computational method to systematically infer and quantify long-range mechanical cell-cell communication through the extracellular matrix (cell-ECM-cell communication). By correlating local ECM remodeling fluctuations, in finite element simulations and live 3D imaging of fibroblasts embedded in fibrin gels, our method matched pairs of communicating cells with high accuracy, and identified whether and to what extent one cell was influenced by its communication partner. Using this method, we revealed that cells actively respond to the mechanical signal that they sense from the other cell, amplifying the formation of a dense fibrin band between the communicating cells. Our method sets the stage to measure the fundamental aspects of intercellular long-range mechanical communication in physiological contextes and may provide a new functional readout for high content 3D image-based screening.