Directional cues in the tumor microenvironment due to cell contraction against aligned collagen fibers.
Directional cues in the tumor microenvironment due to cell contraction against aligned collagen fibers.
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DOI：
10.1016/j.actbio.2021.04.053
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发表时间：
2021-07-15
影响因子：
9.7
通讯作者：
Ponik SM
中科院分区：
文献类型：
--
作者：
Szulczewski JM;Inman DR;Proestaki M;Notbohm J;Burkel BM;Ponik SM
众所周知，乳腺肿瘤微环境中的胶原蛋白排列提供了推动疾病进展的生物物理学线索。许多机制研究已经证明，肿瘤细胞的行为是由胶原蛋白基质的结构和刚度驱动的。然而，3D胶原微环境内的机械性能，特别是在细胞尺度上，仍然定义不清。为了研究局部胶原结构的细胞级机械线索，我们采用了乳腺肿瘤微环境的活体成像和具有无细胞pNIPAAm微球和MDA-MB-231乳腺癌细胞的3D胶原凝胶系统的组合。在体内肿瘤微环境中，胶原纤维的位移被确定为响应于肿瘤细胞迁移通过基质基质。为了进一步研究对齐的纤维结构中的细胞尺度刚度和细胞诱导的纤维变形的传播，将胶原结构的精确控制与测量胶原纤维网络的机械性能的创新方法相结合。这种方法揭示了高达35倍的差异，定向细胞规模的刚度所造成的收缩对对齐的纤维。此外，矩阵的局部各向异性显着改变收缩引起的纤维位移随距离衰减的速率。总之，我们的研究结果揭示了对齐矩阵中的机械特性，这些矩阵在垂直方向上为细胞提供了显着不同的线索。这些发现得到了肿瘤细胞的机械感知行为的支持，并对组织微环境中的细胞-细胞通信具有重要意义。
It is well established that collagen alignment in the breast tumor microenvironment provides biophysical cues to drive disease progression. Numerous mechanistic studies have demonstrated that tumor cell behavior is driven by the architecture and stiffness of the collagen matrix. However, the mechanical properties within a 3D collagen microenvironment, particularly at the scale of the cell, remain poorly defined. To investigate cell-scale mechanical cues with respect to local collagen architecture, we employed a combination of intravital imaging of the mammary tumor microenvironment and a 3D collagen gel system with both acellular pNIPAAm microspheres and MDA-MB-231 breast carcinoma cells. Within the in vivo tumor microenvironment, the displacement of collagen fiber was identified in response to tumor cells migrating through the stromal matrix. To further investigate cell-scale stiffness in aligned fiber architectures and the propagation of cell-induced fiber deformations, precise control of collagen architecture was coupled with innovative methodology to measure mechanical properties of the collagen fiber network. This method revealed up to a 35-fold difference in directional cell-scale stiffness resulting from contraction against aligned fibers. Furthermore, the local anisotropy of the matrix dramatically altered the rate at which contractility-induced fiber displacements decayed over distance. Together, our results reveal mechanical properties in aligned matrices that provide dramatically different cues to the cell in perpendicular directions. These findings are supported by the mechanosensing behavior of tumor cells and have important implications for cell-cell communication within the tissue microenvironment.
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影响因子：
3.9
作者：
Notbohm, Jacob;Lesman, Ayelet;Ravichandran, Guruswami
通讯作者：
Ravichandran, Guruswami
影响因子：
2.4
作者：
Proestaki, M.;Ogren, A.;Notbohm, J.
通讯作者：
Notbohm, J.
影响因子：
8
作者：
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通讯作者：
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影响因子：
11.2
作者：
Grossman, Moran;Ben-Chetrit, Nir;Sagi, Irit
通讯作者：
Sagi, Irit
影响因子：
2.9
作者：
Motte, Stephanie;Kaufman, Laura J.
通讯作者：
Kaufman, Laura J.