Self-Assembly of Mesoscale Collagen Architectures and Applications in 3D Cell Migration.
Self-Assembly of Mesoscale Collagen Architectures and Applications in 3D Cell Migration.
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DOI：
10.1016/j.actbio.2022.11.011
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发表时间：
2022-11
影响因子：
9.7
通讯作者：
Chang Liu;Ryan Y. Nguyen;Gabriela A Pizzurro;Xingjian Zhang;Xiangyu Gong;Alejandro Rossello Martinez;M. Mak
中科院分区：
文献类型：
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作者：
Chang Liu;Ryan Y. Nguyen;Gabriela A Pizzurro;Xingjian Zhang;Xiangyu Gong;Alejandro Rossello Martinez;M. Mak
3D体外肿瘤模型最近被研究，因为它们可以概括肿瘤微环境中的关键特征。在这些模型中，仿生支架的重建至关重要。然而，目前的大多数方法侧重于调制局部属性，例如微米和纳米尺度的地形，而没有捕捉到全球毫米或中间中尺度特征。在这里，我们介绍了一种通过破坏纤维形成和通过机械搅拌来调节凝胶过程来调节I型胶原基细胞外基质结构的方法。用这种方法，我们产生了更大规模的增厚和波浪状的胶原蛋白支架，同时具有全局柔软性。增厚的胶原片与疏松的胶原网相互连接，与肿瘤间质中的胶原蛋白结构高度相似。这种增厚的胶原蛋白网络促进了肿瘤细胞的扩散。此外，这种新型的修饰支架还引发了肿瘤细胞的形态和迁移行为的差异。总之，我们改变胶原结构的方法为详细研究细胞在生理相关生物过程中的行为奠定了新的途径。肿瘤的特征与伤口愈合的特征高度重叠。为了模拟肿瘤环境，胶原基支架被广泛使用。这些支架专注于调节微尺度的地形和力学，与活的建筑相比，缺乏全球建筑的相似性。在这里，我们介绍了一种厚胶原束，它模仿人类皮肤疤痕中的细胞外基质结构。这些加厚的胶原束是长长的波浪形的，同时具有全球性的柔软。这种胶原蛋白结构施加的空间限制较少，并促进了肿瘤细胞的扩散。我们的发现展示了细胞行为和细胞间相互作用的独特图景，突出了胶原蛋白结构和肿瘤微环境的空间异质性的重要性。
3Din vitrotumor models have recently been investigated as they can recapitulate key features in the tumor microenvironment. Reconstruction of a biomimetic scaffold is critical in these models. However, most current methods focus on modulating local properties, e.g. micro- and nano-scaled topographies, without capturing the global millimeter or intermediate mesoscale features. Here we introduced a method for modulating the collagen I-based extracellular matrix structure by disruption of fibrillogenesis and the gelation process through mechanical agitation. With this method, we generated collagen scaffolds that are thickened and wavy at a larger scale while featuring global softness. Thickened collagen patches were interconnected with loose collagen networks, highly resembling collagen architecture in the tumor stroma. This thickened collagen network promoted tumor cell dissemination. In addition, this novel modified scaffold triggered differences in morphology and migratory behaviors of tumor cells. Altogether, our method for altered collagen architecture paves new ways for studying in detail cell behavior in physiologically relevant biological processes.Statement of significanceTumor progression usually involves chronic tissue damage and repair processes. Hallmarks of tumors are highly overlapped with those of wound healing. To mimic the tumor milieu, collagen-based scaffolds are widely used. These scaffolds focus on modulating microscale topographies and mechanics, lacking global architecture similarity compared within vivoarchitecture. Here we introduced one type of thick collagen bundles that mimics ECM architecture in human skin scars. These thickened collagen bundles are long and wavy while featuring global softness. This collagen architecture imposes fewer steric restraints and promotes tumor cell dissemination. Our findings demonstrate a distinct picture of cell behaviors and intercellular interactions, highlighting the importance of collagen architecture and spatial heterogeneity of the tumor microenvironment.