MAPPING 3D MECHANICAL STRAINS DURING TISSUE FORMATION WITH A NOVEL FIBRONECTIN-BASED NANOMECHANICAL BIOSENSOR

In developing tissue, mechanical forces are integral to a range of processes including cell differentiation, tissue morphogenesis, electrophysiology and contractility, but exact roles remain unknown. When mechanical forces are perturbed by experimental intervention or developmental abnormalities, their disruption can lead to congenital defects and disease. To date, tissue-level mechanical strains have been estimated by computational modeling, or by utilizing oil microdroplets as coarse-grained force sensors (1-2). Both methods lack ideal capabilities, which are (i) direct measurement of strain, (ii) at high spatial resolution over time, and (iii) with minimal perturbation of the system. We hypothesized that an extracellular matrix protein-based mechanical biosensor could measure the magnitude, direction and developmental timing of cell-generated strains within developing tissues and organs.Here we fabricated, calibrated and tested a fluorescently labeled fibronectin (FN)-based nano-mechanical biosensor (NMBS), which when applied to a tissue can deform in 3-D to provide a fluorescence-based strain readout during morphogenesis