Loops versus lines and the compression stiffening of cells
Loops versus lines and the compression stiffening of cells
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DOI：
10.1039/c9sm01627a
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发表时间：
2020-05-14
期刊：
影响因子：
3.4
通讯作者：
Schwarz, J. M.
中科院分区：
文献类型：
--
作者：
Gandikota, M. C.;Ogoda, Katarzyna P.;Schwarz, J. M.
动物和植物组织都表现出非线性流变现象，称为压缩硬化，或随着单轴压缩应变的增加而增加模量。这种现象是否存在于构成组织的单细胞中？人们期望单个细胞压缩软化，因为基于半柔性生物聚合物的细胞骨架网络保持细胞的机械完整性，并且体外半柔性生物聚合物网络通常压缩软化。相反，我们发现，小鼠胚胎成纤维细胞（mEFs）压缩单轴压缩下，通过原子力显微镜研究。为了理解这一发现，我们揭示了几个潜在的机制压缩硬化。首先，我们研究了一个单一的半柔性聚合物环路建模的肌动球蛋白皮层封闭的粘性介质建模为不可压缩流体。其次，我们研究了一个二维的半柔性聚合物/纤维网络穿插面积守恒的循环，这是一个代理囊泡和基于流体的细胞器。第三，我们研究了二维纤维网络的角度约束的交联，即半柔性回路的网格规模。在后两种情况下，环充当纤维网络上的几何约束，以通过增加的角度相互作用来帮助纤维网络。我们发现，单个半柔性聚合物环模型与实验细胞压缩硬化发现一致，直到约35%的压缩应变后，散装纤维网络效应可能会有所贡献。我们还发现，对于具有面积守恒环模型的纤维网络，应力-应变曲线对面积守恒环的填充分数和尺寸分布敏感，从而在不同的细胞类型中产生机械指纹。最后，我们将此模型与纤维蛋白网络与珠子交织的实验进行了比较，并讨论了在组织尺度上单细胞压缩硬化的影响。
Both animal and plant tissue exhibit a nonlinear rheological phenomenon known as compression stiffening, or an increase in moduli with increasing uniaxial compressive strain. Does such a phenomenon exist in single cells, which are the building blocks of tissues? One expects an individual cell to compression soften since the semiflexible biopolymer-based cytoskeletal network maintains the mechanical integrity of the cell and in vitro semiflexible biopolymer networks typically compression soften. To the contrary, we find that mouse embryonic fibroblasts (mEFs) compression stiffen under uniaxial compression via atomic force microscopy studies. To understand this finding, we uncover several potential mechanisms for compression stiffening. First, we study a single semiflexible polymer loop modeling the actomyosin cortex enclosing a viscous medium modeled as an incompressible fluid. Second, we study a two-dimensional semiflexible polymer/fiber network interspersed with area-conserving loops, which are a proxy for vesicles and fluid-based organelles. Third, we study two-dimensional fiber networks with angular-constraining crosslinks, i.e. semiflexible loops on the mesh scale. In the latter two cases, the loops act as geometric constraints on the fiber network to help stiffen it via increased angular interactions. We find that the single semiflexible polymer loop model agrees well with the experimental cell compression stiffening finding until approximately 35% compressive strain after which bulk fiber network effects may contribute. We also find for the fiber network with area-conserving loops model that the stress-strain curves are sensitive to the packing fraction and size distribution of the area-conserving loops, thereby creating a mechanical fingerprint across different cell types. Finally, we make comparisons between this model and experiments on fibrin networks interlaced with beads as well as discuss implications for single cell compression stiffening at the tissue scale.