Sensing force with interlocked molecules

拉力影响多种重要的细胞过程，包括细胞分裂、干细胞分化和基因表达。在组织水平上，这些力量在形态发生、伤口愈合、免疫反应甚至癌症转移等病理过程中起着至关重要的作用。然而，由于缺乏测量活组织内细胞内力的技术，我们对体内力如何影响细胞功能的理解非常有限。迄今为止，小分子力传感器已用于膜，遗传编码张力传感器也已开发出来，但由于灵敏度低，它们在体内的应用迄今为止受到限制。在分子水平上，机械力扭曲、弯曲和拉伸化学键的独特能力导致了机械致变色分子的发展，这些分子在合成材料中充当空间敏感分子探针或微裂纹传感器。化学机械传感器为这个问题提供了一个潜在的强大解决方案，但尚未被转化为生物系统。在这里，我们将采取多学科的方法来弥补这一差距，并致力于开发和测试适用于测量活组织张力的新型化学力传感器。

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.