McLeod Claire, Higgins John, Miroshnikova Yekaterina, Liu Rachel, Garrett Aliesha, Sarang-Sieminski Alisha L
Franklin W. Olin College of Engineering, Needham, MA 02492, USA.
J Biomech Eng. 2013 Jul 1;135(7):71002. doi: 10.1115/1.4023984.
The formation of microvascular networks (MVNs) is influenced by many aspects of the microenvironment, including soluble and insoluble biochemical factors and the biophysical properties of the surrounding matrix. It has also become clear that a dynamic and reciprocal interaction between the matrix and cells influences cell behavior. In particular, local matrix remodeling may play a role in driving cellular behaviors, such as MVN formation. In order to explore the role of matrix remodeling, an in vitro model of MVN formation involving suspending human umbilical vein endothelial cells within collagen hydrogels was used. The resulting cell and matrix morphology were microscopically observed and quantitative metrics of MVN formation and collagen gathering were applied to the resulting images. The macroscopic compaction of collagen gels correlates with the extent of MVN formation in gels of different stiffness values, with compaction preceding elongation leading to MVN formation. Furthermore, the microscopic analysis of collagen between cells at early timepoints demonstrates the alignment and gathering of collagen between individual adjacent cells. The results presented are consistent with the hypothesis that endothelial cells need to gather and align collagen between them as an early step in MVN formation.
微血管网络（MVNs）的形成受到微环境诸多方面的影响，包括可溶性和不可溶性生化因子以及周围基质的生物物理特性。同样清楚的是，基质与细胞之间动态且相互的相互作用会影响细胞行为。特别是，局部基质重塑可能在驱动细胞行为（如MVN形成）中发挥作用。为了探究基质重塑的作用，使用了一种MVN形成的体外模型，即将人脐静脉内皮细胞悬浮于胶原水凝胶中。通过显微镜观察所得的细胞和基质形态，并将MVN形成和胶原聚集的定量指标应用于所得图像。胶原凝胶的宏观压实与不同刚度值凝胶中MVN形成的程度相关，压实先于伸长导致MVN形成。此外，在早期时间点对细胞间胶原的显微镜分析表明，单个相邻细胞之间的胶原排列和聚集。所呈现的结果与以下假设一致，即内皮细胞需要在它们之间聚集和排列胶原，作为MVN形成的早期步骤。
