The conventional thinking in cell biology, which often assumes that cells communicate mostly via bio-chemical signalling, has recently been challenged with several examples where mechanical rather than chemical cues play an important role in development, physiology and disease. Biological cells continually exert forces on their environment, which can vary substantially in magnitude, spatial distribution and temporal evolution. These forces are key to many processes including cell growth, tissue formation, wound healing and the invasion of cancer cells into healthy tissue. Understanding how cellular forces affect the micro-environment hinges on our ability to image them with sufficient local and temporal resolution (e.g. continuously over several days with subcellular spatial resolution), adequate field of view (e.g. to study cell sheets) and relevant sensitivity (typical forces are in the pico to nano Newton range). Despite significant advances made in this area of functional bioimaging over the last years, existing methods still struggle to meet the requirements, thus precluding new commercial opportunities in cell biomechanics.
The CELL-FORCE project worked to demonstrate Elastic Resonator Interference Stress Microscopy (ERISM) as a new microscopy method that allows direct, robust and non-destructive imaging of forces associated with various mechanical cell-substrate interactions, and validate its commercial feasibility. The greatly increased sensitivity offered by ERISM over other methods was used to allow accurate measurements of vertical forces and of cells exerting only weak force. Moreover, with a low light intensity requirement and no need to detach cells after a measurement, using ERISM makes it possible to take long-term measurements of multiple cells without photodamage and facilitates downstream applications such as immunostaining.
