PT - JOURNAL ARTICLE AU - Daniel J. Shiwarski AU - Joshua W. Tashman AU - Alkiviadis Tsamis AU - Jacqueline M. Bliley AU - Malachi A. Blundon AU - Edgar Aranda-Michel AU - Quentin Jallerat AU - John M. Szymanski AU - Brooke M. McCartney AU - Adam. W. Feinberg TI - Fibronectin-Based Nanomechanical Biosensors to Map 3D Strains in Live Cells and Tissues AID - 10.1101/2020.02.11.943696 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.02.11.943696 4099 - http://biorxiv.org/content/early/2020/02/12/2020.02.11.943696.short 4100 - http://biorxiv.org/content/early/2020/02/12/2020.02.11.943696.full AB - Mechanical forces are integral to a wide range of cellular processes including migration, differentiation and tissue morphogenesis; however, it has proved challenging to directly measure strain at high spatial resolution and with minimal tissue perturbation. Here, we fabricated, calibrated, and tested a fibronectin (FN)-based nanomechanical biosensor (NMBS) that can be applied to cells and tissues to measure the magnitude, direction, and dynamics of strain from subcellular to tissue length-scales. The NMBS is a fluorescently-labeled, ultrathin square lattice FN mesh with spatial resolution tailored by adjusting the width and spacing of the lattice fibers from 2-100 µm. Time-lapse 3D confocal imaging of the NMBS demonstrated strain tracking in 2D and 3D following mechanical deformation of known materials and was validated with finite element modeling. Imaging and 3D analysis of the NMBS applied to single cells, cell monolayers, and Drosophila ovarioles demonstrated the ability to dynamically track microscopic tensile and compressive strains in various biological applications with minimal tissue perturbation. This fabrication and analysis platform serves as a novel tool for studying cells, tissues, and more complex systems where forces guide structure and function.