Collective forces of tumor spheroids in three-dimensional biopolymer networks
Collective forces of tumor spheroids in three-dimensional biopolymer networks
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DOI：
10.7554/elife.51912
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发表时间：
2020-04-30
期刊：
影响因子：
7.7
通讯作者：
Fabry, Ben
中科院分区：
文献类型：
--
作者：
Mark, Christoph;Grundy, Thomas J.;Fabry, Ben
我们描述了一种用于量化肿瘤球体共同施加在高度非线性三维胶原网络上的收缩力的方法。虽然三维牵引力显微镜的非线性矩阵中的单细胞是计算复杂的，由于可变的细胞形状，在这里，我们利用肿瘤球体的球形对称性，推导出球体收缩性和周围的矩阵变形之间的比例不变的关系。这种关系使我们能够直接将基质变形的大小转化为任意大小的球体的总收缩性。我们表明，我们的方法是准确的应变高达50%，仍然有效，即使是不规则形状的组织样本时，只考虑在远场的变形。最后，我们证明了肿瘤球体的集体力量反映了单个细胞在接种后长达1小时的收缩性，而更长时间尺度上的集体力量则由细胞外基质的机械反馈指导。
We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.