论文标题

3D水凝胶中笼的力细胞的感觉:流变学的角度

What Caging Force Cells Feel in 3D Hydrogels: A Rheological Perspective

论文作者

Ciccone, Giuseppe, Dobre, Oana, Gibson, Graham M., Vassalli, Massimo, Salmeron-Sanchez, Manuel, Tassieri, Manlio

论文摘要

已经确定水凝胶的机械性能控制(茎)细胞的命运。然而,尽管其重要性,但文献中仍然缺少凝胶刚度和细胞行为之间的一对一对应关系。在这项工作中,通过在3D细胞培养物中广泛使用的聚(乙二醇)(PEG)的水凝胶的粘弹性特性,其机械性能可以调节与不同生物组织的机械性能相似 - 通过在不同长度尺度上执行的流变测量。与文献值相比,这项工作的结果表明,常规的大量流变学测量可能会高估水凝胶的刚度,直到数量级。证明这种明显的僵硬是由于测量过程中施加了压缩正常力,这是由凝胶网络的诱导的“张力状态”引起的。此外,结果表明,水凝胶的实际刚度取而代之的是通过被动式视频粒子跟踪(PVPT)微流变测量的方法准确地确定,这些测量是在细胞长度尺度上固有地执行的,并且在没有任何外部施加力的情况下进行。这些结果是测量水凝胶的线性粘弹性特性的方法,这些方法代表了3D水凝胶培养物中细胞所感受到的机械约束。

It is established that the mechanical properties of hydrogels control the fate of (stem) cells. However, despite its importance, a one-to-one correspondence between gels' stiffness and cell behaviour is still missing from literature. In this work, the viscoelastic properties of Poly(ethylene-glycol) (PEG)-based hydrogels - broadly used in 3D cell cultures and whose mechanical properties can be tuned to resemble those of different biological tissues - are investigated by means of rheological measurements performed at different length scales. When compared with literature values, the outcomes of this work reveal that conventional bulk rheology measurements may overestimate the stiffness of hydrogels by up to an order of magnitude. It is demonstrated that this apparent stiffening is caused by an induced 'tensional state' of the gel network, due to the application of a compressional normal force during measurements. Moreover, it is shown that the actual stiffness of the hydrogels is instead accurately determined by means of passive-video-particle-tracking (PVPT) microrheology measurements, which are inherently performed at cells length scales and in absence of any externally applied force. These results underpin a methodology for measuring the linear viscoelastic properties of hydrogels that are representative of the mechanical constraints felt by cells in 3D hydrogel cultures.

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