A Multidisciplinary Bioimaging Platform for Quantitative Force Mapping in the Beating Heart

Physical forces are fundamental drivers of tissue-level biological processes, yet we still lack tools to quantify how subcellular forces drive the collective behaviour of the cell populations forming developing organs, and how this shapes overall architecture and function. The heart is an extraordinary example of this complexity, where the cellular behaviours underpinning heart morphogenesis can only be understood if we can measure the tissue-level forces in the presence of cardiac contractile forces. Progress is frustrated by the absence of any bioimaging technology with the performance and temporal resolution for direct quantitative imaging of intercellular forces in highly dynamic 3D environments such as the beating heart. We are addressing this gap with a purpose-built bioimaging platform to achieve the ambitious goal of mapping the force landscape throughout the beating heart, in a live intact organism. To achieve this we are developing novel optical and computational imaging approaches for single-photon motion-corrected fluorescence lifetime imaging, alongside new optical molecular tension sensors – delivering for the first time subcellular-resolution, whole-organ force imaging in vivo in highly dynamic environments. This will reveal how the intercellular force landscape is modulated by contractile activity, tissue architecture and cell crowding – and the implications for cardiac development and disease.