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成纤维细胞介导的胶原凝胶紧缩的机制和单个成纤维细胞周围的机械小生境。

The mechanisms of fibroblast-mediated compaction of collagen gels and the mechanical niche around individual fibroblasts.

机构信息

Graduate School of Science and Engineering, Yamagata University, Japan.

Graduate School of Science and Engineering, Yamagata University, Japan.

出版信息

Biomaterials. 2014 Sep;35(28):8078-91. doi: 10.1016/j.biomaterials.2014.05.072. Epub 2014 Jun 26.

DOI:10.1016/j.biomaterials.2014.05.072
PMID:24976242
Abstract

Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo.

摘要

成纤维细胞介导的胶原凝胶压实在创伤愈合、细胞命运过程和再生医学研究中受到广泛关注。然而,其潜在的机制和细胞力学环境仍然不清楚。本研究从主要力学相互作用的另一个角度考察了胶原纤维在压实过程中的力学行为,为密集型成纤维细胞的行为提供了一个新的视角。我们将胶原纤维分为三种类型 - 弯曲、拉伸和黏附,并推导出每种类型的力学行为所对应的方程;特别是,基于机械转导系统瞬时哈密顿量的静止状态假设原则,我们最初量化了每个拉伸纤维上所施加的拉伸力。通过对基于这种分类的结构基本模型的仔细验证,我们展示了压实过程的清晰物理图像,定量阐明了微力学环境的全景,并揭示了细胞牵引力和基质弹性之间内在的双相关系。我们的结果还推断了成纤维细胞张力稳态和应力屏蔽的潜在机制。通过这项研究以及对本文提出的假设原则的后续研究,我们期望重新聚焦细胞力学生物学的研究,无论是在体外还是体内。

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