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

Intercellular forces are a crucial driver of embryo and organ morphogenesis, and these forces are particularly complex in highly-mobile tissue such as the beating heart. Given the complex multi-scale interactions shaping cardiac architecture, a holistic approach is essential to understand these tissue-scale biomechanical forces. It is only with the heart beating in its natural context that we can ask: what are the local intercellular forces shaping the beating heart, and how do they integrate with cardiac function to ensure robust cardiac morphogenesis in the embryo? We will develop new bio-imaging technology to answer this question, applying it initially to a zebrafish model of cardiac development. 
 
Although fluorescence microscopy has revolutionised structural imaging, it is much harder to gain insights into the function of constituent cells in situ in a living animal, and understand the forces that drives many cell behaviours. Two critical technological challenges must be solved: how to capture high-quality subcellular images at all in this complex, dynamic environment, and how to measure the intercellular forces present. Recently-emerged FLIM-FRET tension sensing probes and TCSPC array cameras hold exciting potential for tissue-scale cellular force mapping in highly dynamic live environments such as the heart. But refining and applying these underpinning technologies to live beating-heart imaging will require significant new research into computational imaging and probe development. Once developed, we expect our imaging technology to bring new mechanobiological insights in a wide range of dynamic systems encompassing both model organisms and cultured organoids.