Modulus of Fibrous Collagen at the Length Scale of a Cell
Modulus of Fibrous Collagen at the Length Scale of a Cell
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DOI：
10.1007/s11340-018-00453-4
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发表时间：
2019-11-01
影响因子：
2.4
通讯作者：
Notbohm, J.
中科院分区：
文献类型：
--
作者：
Proestaki, M.;Ogren, A.;Notbohm, J.
细胞外基质为组织提供宏观结构支持，并为驻留细胞提供微观机械提示，如硬度。由于这些信号调节基因表达、增殖、分化和运动，因此量化细胞感受到的硬度对于理解细胞行为至关重要。尽管胶原网络的宏观模量可以在均匀拉伸或剪切下测量，但由于纤维网络在细胞尺度上的不均匀性和非线性性质，量化细胞感测的局部刚度仍然是一个挑战。为了应对这一挑战，我们设计了一种实验方法来测量这种规模的胶原纤维网络的模量。我们使用了活性水凝胶（聚N-异丙基丙烯酰胺）的球形颗粒，当加热时收缩，从而向胶原基质施加局部力并模仿细胞的收缩力。在测量胶原纤维网络中颗粒的体积模量和收缩后，我们应用纤维材料的非线性模型来计算每个颗粒周围局部区域的模量。我们发现，在这个长度尺度的模量是高度异质性的，与模量变化的3倍。此外，在不同的施加应变值，我们观察到应变硬化和应变软化，表明胶原网络的非线性。因此，这种实验方法可以量化细胞规模的纤维网络中的局部力学性能，同时也考虑了固有的非线性。
The extracellular matrix provides macroscale structural support to tissues as well as microscale mechanical cues, like stiffness, to the resident cells. As those cues modulate gene expression, proliferation, differentiation, and motility, quantifying the stiffness that cells sense is crucial to understanding cell behavior. Whereas the macroscopic modulus of a collagen network can be measured in uniform extension or shear, quantifying the local stiffness sensed by a cell remains a challenge due to the inhomogeneous and nonlinear nature of the fiber network at the scale of the cell. To address this challenge, we designed an experimental method to measure the modulus of a network of collagen fibers at this scale. We used spherical particles of an active hydrogel (poly N-isopropylacrylamide) that contract when heated, thereby applying local forces to the collagen matrix and mimicking the contractile forces of a cell. After measuring the particles' bulk modulus and contraction in networks of collagen fibers, we applied a nonlinear model for fibrous materials to compute the modulus of the local region surrounding each particle. We found the modulus at this length scale to be highly heterogeneous, with modulus varying by a factor of 3. In addition, at different values of applied strain, we observed both strain stiffening and strain softening, indicating nonlinearity of the collagen network. Thus, this experimental method quantifies local mechanical properties in a fibrous network at the scale of a cell, while also accounting for inherent nonlinearity.