Department of Chemical Engineering, McGill University, 3610 University Street, Montreal, QC, H3A 0C5, Canada.
Rosalind and Morris Goodman Cancer Research Centre, McGill University, 160 Pine Ave W, Montreal, QC, H3A 1A3, Canada.
Nat Commun. 2020 Sep 21;11(1):4757. doi: 10.1038/s41467-020-18469-7.
Local tissue mechanics play a critical role in cell function, but measuring these properties at cellular length scales in living 3D tissues can present considerable challenges. Here we present thermoresponsive, smart material microgels that can be dispersed or injected into tissues and optically assayed to measure residual tissue elasticity after creep over several weeks. We first develop and characterize the sensors, and demonstrate that internal mechanical profiles of live multicellular spheroids can be mapped at high resolutions to reveal broad ranges of rigidity within the tissues, which vary with subtle differences in spheroid aggregation method. We then show that small sites of unexpectedly high rigidity develop in invasive breast cancer spheroids, and in an in vivo mouse model of breast cancer progression. These focal sites of increased intratumoral rigidity suggest new possibilities for how early mechanical cues that drive cancer cells towards invasion might arise within the evolving tumor microenvironment.
局部组织力学在细胞功能中起着关键作用，但在活体 3D 组织中以细胞长度尺度测量这些性质可能会带来相当大的挑战。在这里，我们提出了热响应性智能材料微凝胶，可将其分散或注入组织中，并进行光学分析，以测量在几周的蠕变后残余组织弹性。我们首先开发并表征了这些传感器，并证明可以以高分辨率绘制活的多细胞球体的内部机械轮廓，以揭示组织内的广泛硬度范围，这些范围随球体聚集方法的细微差异而变化。然后，我们表明在侵袭性乳腺癌球体和乳腺癌进展的体内小鼠模型中，出乎意料的高硬度的小部位会发展。这些肿瘤内刚性增加的局部部位表明，在不断发展的肿瘤微环境中，驱动癌细胞侵袭的早期机械线索可能会以新的方式出现。
