Cells are constantly exposed to mechanical stimuli that provide important signals which, combined with others from the cellular microenvironment, regulate a plethora of functions at molecular, cellular, and tissue levels. A typical example is the cardiac muscle, the failure of which remains a central health and societal issue. Approaches making it possible to address cell mechanobiology on different spatial and temporal scales within an integrated biological system are still lacking, although this would be of tremendous importance to tackle a great number of various biological processes linked to illnesses such as heart ischemia. OPTO-MECHA-3D is an ingenious new technology to conceptualize cell mechanobiological approaches in 3D ex vivo tissue models. In this project, we aim to develop a dedicated multiscale and multifunctional imaging platform capable of dealing with such 3D models, as well as both interacting with and perturbing them mechanically in a spatially resolved and well-defined fashion. A successful demonstration of the potential of our technology with ex vivo cardiac tissue would represent a major milestone for the future of biomedical research, since OPTO-MECHA-3D has the potential of becoming the standard for studying, not just cardiac function, but various cell mechano-physiological processes that are of interest in many biological fields. The central idea of the project is to associate an intelligent sample holder based on hydrogels that will produce the mechanical stimulus into a light sheet fluorescence microscopy (LSFM) setup that will give access to the response of the cardiac tissue to the stimulus For this, OPTO-MECHA-3D will bond 5 academic teams and an industrial partner: ITAV (CNRS laboratory, specialist of light sheet fluorescence microscopy), I2MC (INSERM unit, specialized in cardiovascular diseases), IMRCP (CNRS unit, expertise in hydrogel synthesis and photoresponsive systems), ICFO in Spain (specialist of photonic microscopy) and FHNW in Switzerland (expertise in laser development). The last partner is Kaivogen Inc, a finnish company specialized in up-converting nanoparticles, which will be incorporated in the hydrogels. This consortium enables to join together the different disciplines which are essential for the carrying out of the work, but the ANR funding would enable the consortium to get more optimized (possibly by addition of one or 2 new partners), answering critical comments from two former proposal submissions in 2016 and 2017.