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Mapping cellular-scale internal mechanics in 3D tissues with thermally responsive hydrogel probes.
Nature Communications ( IF 16.6 ) Pub Date : 2020-09-21 , DOI: 10.1038/s41467-020-18469-7
Stephanie Mok 1 , Sara Al Habyan 2 , Charles Ledoux 1 , Wontae Lee 1 , Katherine N MacDonald 1 , Luke McCaffrey 2 , Christopher Moraes 1, 2, 3
Affiliation  

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.



中文翻译:

使用热响应水凝胶探针绘制 3D 组织中的细胞尺度内部力学。

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特性可能会带来相当大的挑战。在这里,我们提出了热响应的智能材料微凝胶,可以将其分散或注射到组织中,并通过光学分析来测量蠕变数周后的残余组织弹性。我们首先开发和表征传感器,并证明活多细胞球体的内部机械剖面可以以高分辨率绘制,以揭示组织内的广泛刚度,这些刚度随球体聚集方法的细微差异而变化。然后我们表明,在浸润性乳腺癌球体和乳腺癌进展的体内小鼠模型中,出现了意外高刚性的小部位。

更新日期:2020-09-21
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