PT - JOURNAL ARTICLE AU - Nils M. Kronenberg AU - Philipp Liehm AU - Anja Steude AU - Johanna A. Knipper AU - Jessica G. Borger AU - Giuliano Scarcelli AU - Kristian Franze AU - Simon J. Powis AU - Malte C. Gather TI - Long-Term Imaging of Cellular Forces with High Precision by Elastic Resonator Interference Stress Microscopy AID - 10.1101/118554 DP - 2017 Jan 01 TA - bioRxiv PG - 118554 4099 - http://biorxiv.org/content/early/2017/03/20/118554.short 4100 - http://biorxiv.org/content/early/2017/03/20/118554.full 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.