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

Physical forces are fundamental drivers of tissue-level biological processes.

Important questions remain unanswered about 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. However, with recent advances in several enabling technologies, we now foresee a route to this ambitious goal.

We propose a multidisciplinary bioimaging platform to map forces throughout the beating heart, in a live intact organism.

To achieve this we will research a novel optical and computational imaging approach for single-photon motion correction, delivering for the first time subcellular- resolution, whole-organ force imaging in vivo highly dynamic environments.

This will enable us to discern how the intercellular force landscape is modulated by contractile activity, tissue architecture and cell crowding – and understand the implications for cardiac development and disease.