Characterizing the time-dependent mechanical properties of cells is not only necessary to determine how they deform, but also to fully understand how external forces trigger biochemical-signaling cascades to govern their behavior. Presently mechanical properties are largely assessed by applying local shear or compressive forces on single cells in isolation grown on non-physiological 2D surfaces. In comparison, we developed the microfabricated vacuum actuated stretcher to measure tensile loading of 3D multicellular ‘microtissue’ cultures. With this approach, we assessed here the time-dependent stress relaxation and recovery responses of microtissues, and quantified the spatial remodeling that follows step length changes. Unlike previous results, stress relaxation and recovery in microtissues measured over a range of step amplitudes and pharmacological treatments followed a stretched exponential behavior describing a broad distribution of inter-related timescales. Furthermore, despite a performed compendium of experiments, all responses led to a single linear relationship between the residual elasticity and degree of stress relaxation, suggesting that these mechanical properties are coupled through interactions between structural elements and the association of cells with their matrix. Lastly, although stress relaxation could be quantitatively and spatially linked to recovery, they differed greatly in their dynamics; while stress recovery behaved as a linear process, relaxation time constants changed with an inverse power law with step size. This assessment of microtissues offers insights into how the collective behavior of cells in a 3D collagen matrix generate the dynamic mechanical properties of tissues, which is necessary to understanding how cells deform and sense mechanical forces in the body.

中文翻译：

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机械应变的3D微组织中随时间变化的应力松弛和恢复

表征细胞随时间变化的机械特性不仅是确定它们如何变形的必要条件，而且是充分理解外力如何触发生化信号级联以控制其行为的必要条件。目前，通过在非生理2D表面上隔离生长的单个细胞上施加局部剪切力或压缩力来很大程度上评估机械性能。相比之下，我们开发了微型真空启动担架，用于测量3D多细胞“微组织”培养物的拉伸负荷。通过这种方法，我们在这里评估了随时间变化的应力松弛和微组织的恢复响应，并量化了步长变化后的空间重塑。与以前的结果不同 在一定幅度范围内的阶跃幅度和药物治疗中，微组织中的应力松弛和恢复遵循拉伸指数行为，描述了相互关联的时标的广泛分布。此外，尽管进行了实验纲要，但所有响应都导致了残余弹性和应力松弛程度之间的线性关系，这表明这些机械性能是通过结构元素之间的相互作用以及细胞与其基质的缔合而耦合的。最后，尽管应力松弛可以在数量和空间上与恢复相关，但它们的动力学差异很大。当应力恢复表现为线性过程时，松弛时间常数随步长的反幂定律而变化。