Title: Detecting force transmission pathways in 3D fibrin networks
Abstract: Cells receive mechanical cues from their surroundings. Of particular interest are 3D fibrous matrices, offering a more physiological microenvironment. The path of force transmission through fibrous extracellular matrices is difficult to predict but of great importance to cell biology. Force transmission in bulk fibrous matrices is well studied, but the local fiber network response to forces is yet to be fully understood. Modelling has provided insight into how these 3D fibrous networks transmit forces, however direct measurement of force transmission through these networks remains a challenge. Here we detect which fibers respond to an applied force using fluorescence confocal microscopy and optical tweezers in a 3D fibrin hydrogel. Embedded microbeads are oscillated by optical tweezers at low frequency to explore force transmission while avoiding the nonlinearity of the network observed at higher frequencies. Pixel intensity fluctuations in time are used to detect the subset of fibers within a local network that oscillate in phase with the microbead at the drive frequency, and thus carry tension. With some extension of this approach, the results can be used to further inform our understanding of fibrous biological materials at the mesoscale.