Collagen oligomers modulate physical and biological properties of three-dimensional self-assembled matrices.
Collagen oligomers modulate physical and biological properties of three-dimensional self-assembled matrices.
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DOI：
10.1002/bip.21537
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发表时间：
2011-02
期刊：
影响因子：
2.9
通讯作者：
Voytik-Harbin, S. L.
中科院分区：
文献类型：
--
作者：
Bailey, J. L.;Critser, P. J.;Whittington, C.;Kuske, J. L.;Yoder, M. C.;Voytik-Harbin, S. L.
关键词：
阐明胶原原纤维组装和基质诱导的细胞命运指导的机制将有助于设计和扩大使用这种生物聚合物的研究和临床应用。在这里，我们定义了I型胶原低聚物如何影响体外聚合动力学以及原纤维的微观结构和形成的基质的机械性能。从酸溶猪皮胶原中分离出单体和低聚物，并用于生成单体/低聚物含量或平均聚合物分子量（AMW）不同的制剂。聚合半衰期随着胶原AMW的增加而降低，并且紧密地延迟时间，表明低聚物有效地充当成核位点。此外，增加AMW产生的矩阵与增加原纤间的分支，并没有相关的影响原纤密度或直径。这些微观结构的变化增加了矩阵的刚度证明了在剪切存储和压缩模量的增加。最后，通过培养的内皮集落形成细胞感知基质物理性质的相关变化并改变空泡和毛细血管样网络形成的能力，证明了调节胶原AMW的生物相关性。这项工作记录了低聚物作为另一种生理相关的设计参数的重要性，用于开发和标准化可聚合胶原蛋白制剂，用于细胞培养，再生医学和工程组织应用。
Elucidation of mechanisms underlying collagen fibril assembly and matrix-induced guidance of cell fate will contribute to the design and expanded use of this biopolymer for research and clinical applications. Here, we define how Type I collagen oligomers affect in-vitro polymerization kinetics as well as fibril microstructure and mechanical properties of formed matrices. Monomers and oligomers were fractionated from acid-solubilized pig skin collagen and used to generate formulations varying in monomer/oligomer content or average polymer molecular weight (AMW). Polymerization half-times decreased with increasing collagen AMW and closely paralleled lag times, indicating that oligomers effectively served as nucleation sites. Furthermore, increasing AMW yielded matrices with increased interfibril branching and had no correlative effect on fibril density or diameter. These microstructure changes increased the stiffness of matrices as evidenced by increases in both shear storage and compressive moduli. Finally, the biological relevance of modulating collagen AMW was evidenced by the ability of cultured endothelial colony forming cells to sense associated changes in matrix physical properties and alter vacuole and capillary-like network formation. This work documents the importance of oligomers as another physiologically-relevant design parameter for development and standardization of polymerizable collagen formulations to be used for cell culture, regenerative medicine, and engineered tissue applications.
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