RT Journal Article SR Electronic T1 Long-Term Imaging of Cellular Forces with High Precision by Elastic Resonator Interference Stress Microscopy JF bioRxiv FD Cold Spring Harbor Laboratory SP 118554 DO 10.1101/118554 A1 Nils M. Kronenberg A1 Philipp Liehm A1 Anja Steude A1 Johanna A. Knipper A1 Jessica G. Borger A1 Giuliano Scarcelli A1 Kristian Franze A1 Simon J. Powis A1 Malte C. Gather YR 2017 UL http://biorxiv.org/content/early/2017/03/20/118554.abstract AB Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to online analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell-substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic Resonator Interference Stress Microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity). This enables investigation of minute vertical stresses (<1 Pa) involved in podosome protrusion, protein specific cell-substrate interaction and amoeboid migration through spatial confinement in real time. ERISM requires no zero-force reference and avoids phototoxic effects, which facilitates force monitoring over multiple days and at high frame rates and eliminates the need to detach cells after measurements. This allows observation of slow processes like differentiation and further investigation of cells, e.g. by immunostaining.