Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures.
Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures.
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DOI：
10.1039/c5ib00207a
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Verbridge SS
中科院分区：
文献类型：
--
作者：
Hosseini Y;Agah M;Verbridge SS
模拟细胞-组织相互作用的实验工具可能会为理解和治疗癌症开辟新的途径。虽然最近已经研究了肿瘤细胞的机械特性和侵袭调节，但在肿瘤血管动力学的背景下，这些受到的关注较少。在这篇文章中，我们研究了血管生成过程中内皮细胞侵入其周围细胞外基质（ECM）所遇到的结构表面之间的相互作用。为此目的，我们已经制造了圆形和尖锐的几何形状，在胶原蛋白水凝胶中具有各种曲率和锐度指数，在很宽的刚度范围内，以模拟从正常到肿瘤组织的不同微环境。然后，我们在这些结构上培养内皮细胞，以研究细胞和ECM之间的双向相互作用。我们已经观察到，细胞侵入频率是从具有最高的锐度和曲率指数的结构较高，而有趣的是，侵入对局部微观几何形状的依赖性是最强的最高密度矩阵。值得注意的是，具有最高侵入长度的结构与侧部结构的较高变形相关联，这可能与牵引力激活的信号传导有关，这表明需要进一步研究。我们已经注意到，圆形结构更有利于细胞粘附，并且在某些情况下，圆形结构比尖锐结构更快地驱动细胞侵入。这些结果突出了内皮细胞感知ECM几何形状的微小变化的能力，并以基质侵袭和变形的平衡来响应，具有反馈机制的潜在影响，该反馈机制可能增强血管异常以响应肿瘤诱导的ECM改变。
Experimental tools to model cell-tissue interactions will likely lead the way to new ways to both understand and treat cancer. While the mechanical properties and regulation of invasion have been recently studied for tumor cells, these have received less attention in the context of tumor vascular dynamics. In this article, we have investigated the interaction between the surfaces of structures encountered by endothelial cells invading their surrounding extracellular matrix (ECM) during angiogenesis. For this purpose, we have fabricated round and sharp geometries with various curvature and sharpness indices in collagen hydrogel at a wide range of stiffness to mimic different microenvironments varying from normal to tumor tissues. We have then cultured endothelial cells on these structures to investigate the bi-directional interaction between the cells and ECM. We have observed that cell invasion frequency is higher from the structures with the highest sharpness and curvature index, while interestingly the dependence of invasion on local micro-geometry is strongest for the highest density matrices. Notably, structures with the highest invasion length are linked with higher deformation of side structures, which may be related to traction force-activated signaling suggesting further investigation. We have noted that round structures are more favorable for cell adhesion and in some cases round structures drive cell invasion faster than sharp ones. These results highlight the ability of endothelial cells to sense small variations in ECM geometry, and to respond with a balance of matrix invasion as well as deformation, with potential implications for feedback mechanisms that may enhance vascular abnormality in response to tumor-induced ECM alterations.