Lesman, A. | Search bioRxiv

bioRxiv2022

Probing Local Force Propagation in Tensed Fibrous Gels

Fibrous hydrogels are a key component of soft animal tissues. They support cellular functions and facilitate efficient mechanical communication between cells. Due to their nonlinear mechanical properties, fibrous materials display non-trivial force propagation at the microscale, that is enhanced compared to that of linear-elastic materials. In the body, tissues are constantly subjected to external loads that tense or compress them, modifying their micro-mechanical properties into an anisotropic state. However, it is unknown how force propagation is modified by this isotropic-to-anisotropic transition. Here, we directly measure force propagation in tensed fibrin hydrogels. Local perturbations are induced by oscillating microspheres using optical tweezers. We use both 1-point and 2-point microrheology to simultaneously measure both the shear modulus and force propagation. We suggest a mathematical framework to quantify anisotropic force propagation trends. We show that force propagation becomes anisotropic in tensed gels, with, surprisingly, stronger response to perturbations perpendicular to the axis of tension. Our results suggest that under external loads, there are favoured directions of mechanical communication between cells in a tissue. Importantly, we also find that external tension increases the range of force transmission by altering the power-law exponent governing the decay of oscillations with distance from the perturbation. We end with a discussion of possible implications and future directions for research.

biophysics↗

bioRxiv2020

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

Cells sense, manipulate and respond to their mechanical microenvironment in a plethora of physiological processes, yet the understanding of how cells transmit, receive and interpret environmental cues to communicate with distant cells is severely limited due to lack of tools to quantitatively infer the complex tangle of dynamic cell-cell interactions in complicated environments. We present a computational method to systematically infer and quantify long-range cell-cell force transmission through the extracellular matrix (cell-ECM-cell communication) by correlating ECM remodeling fluctuations in between communicating cells and demonstrating that these fluctuations contain sufficient information to define unique signatures that robustly distinguish between different pairs of communicating cells. We demonstrate our method with finite element simulations and live 3D imaging of fibroblasts and cancer cells embedded in fibrin gels. While previous studies relied on the formation of a visible fibrous band extending between cells to inform on mechanical communication, our method detected mechanical propagation even in cases where visible bands never formed. We revealed that while contractility is required, band formation is not necessary, for cell-ECM-cell communication, and that mechanical signals propagate from one cell to another even upon massive reduction in their contractility. Our method sets the stage to measure the fundamental aspects of intercellular long-range mechanical communication in physiological contexts and may provide a new functional readout for high content 3D image-based screening. The ability to infer cell-ECM-cell communication using standard confocal microscopy holds the promise for wide use and democratizing the method.

cell biology↗