Sensing force with interlocked molecules

Tensile forces influence a variety of important cellular processes including cell division, stem cell differentiation and gene expression. At the tissue level these forces play a crucial role in morphogenesis, wound healing, the immune response and even in pathological processes such as cancer metastasis. However, our understanding of how force influences cell function in vivo is extremely limited due to a lack of techniques to measure intracellular forces within live tissues. To date, small-molecule force sensors have been used in membranes and genetically encoded tension sensors have been developed, but their use in vivo has so far been limited due to their low sensitivity. At the molecular level, the unique ability of mechanical force to distort, bend and stretch chemical bonds has led to the development of mechanochromic molecules acting as spatially sensitive molecular probes or micro-crack sensors in synthetic materials. Chemical mechanosensors offer a potentially powerful solution to this problem but have yet to be translated into biological systems. Here we will take a multidisciplinary approach to bridge this gap and aim to develop and test novel chemical force sensors suitable for measuring tensile forces in live tissues.