“BrillFM”: a correlative micro- and spectro-scope to optically probe cellular dynamics and biomechanics

The mechanical interplay between neighbouring biological substances is fundamental to life processes from the sub-cellular to whole organism scales. However, defining the complex relationships between biomechanical forces and processes in living samples has been limited by current technologies and approaches. This application seeks to overcome this barrier, building the UK’s first correlative fluorescence microscopy-spectroscopy platform – “BrillFM”. This accessible novel multi-modal imaging platform will allow the live, non-invasive, and in vivo examination, relating cellular dynamics with biomechanics. Specifically, we will combine a Cellsense Discoverer Brillouin light scattering (BLS) spectrometer with a Nikon Ti2 W1 SoRa Spinning Disk and iLAS fluorescence microscope (FM). In contrast to other biomechanical probing tools, BLS is optical, so requires no physical contact with the sample. It is also compatible with existing live sample preparation methods. Therefore, the same cell or tissue can be probed to provide readouts of both material properties (such as ‘stiffness’ and ‘elasticity’) and outputs relating to fluorescently-labelled cellular structures. BrillFM will therefore uniquely provide insights into the complex interplay between cellular processes and their biomechanical environments. The University of Exeter’s Biosciences department, Living Systems Institute, Clinical and Biomedical Sciences, and Biomedical Physics groups are renowned for their contributions to the fundamental understanding of our natural world. They routinely working across disciplines to generate biological knowledge which can be used to benefit some of society’s greatest challenges. Its Bioimaging Centre functions as a hub in the Southwest, providing the region with supported access to advanced microscopy systems. The unique combination of state-of-the-art transformative technology, the expertise of our applicant team (consisting of experts in biology, microscopy and spectroscopy), and the reach of our collaborative partners (regional, national and international), will provide novel insights into the fundamental rules of life, facilitating and accelerating discoveries in plant and animal cell, and developmental biology, and biophysics. Our aims and objectives include: Establishing a transformative technology platform to provide novel insights into the biophysical rules of life. Enabling research within the BBSRC strategic challenge of sustainable agriculture and food. Provide unique educational, training and talent recruitment opportunities for students, early career researchers and senior academic levels. As BrillFM will provide quantitative outputs not possible with other systems in the UK, it will have many potential applications and benefits for a wide range of research in Exeter and beyond. For example: Understanding the influence of stress (including climate change and pathogens) upon plant biomechanics to provide insights for food security and climate change mitigation strategies. Provide novel insights into the interplay and influence of biomechanical environments in cell fate decisions, cell migration and organ morphogenesis, to better understand the biophysical rules of life. Investigate how pathological stresses disrupt cellular biomechanics to probe the cellular mechanisms underlying organismal health. By supporting the UK’s first correlative BLS and FM system, this proposal will provide a significant increase in our ability to understand the complex and fundamental role biomechanics play in biology. The University of Exeter, and applicant team, are uniquely placed to deliver this transformative technology, delivering impact relevant to understanding the fundamental rules of life and towards society’s greatest challenges. This world class capability will provide a boost to Exeter’s ability to attract, train, and retain, the very best researchers working towards BBSRC strategic objectives.