Narita Takayuki, Kondo Misaki, Oishi Yushi
Department of Chemistry and Applied Chemistry, Saga University, 1 Honjo, Saga 840-8502, Japan.
ACS Omega. 2021 Dec 18;7(1):1014-1020. doi: 10.1021/acsomega.1c05601. eCollection 2022 Jan 11.
Shapes and patterns observed in internal organs and tissues are reproducibly and robustly produced over a long distance (up to millimeters in length). The most fundamental remaining question is how these long geometries of shape and pattern form arise from the genetic message. Recent studies have demonstrated that extracellular matrix (ECM) critically participates as a structural foundation on which cells can organize and communicate. ECMs may be a key to understanding the underlying mechanisms of long-distance patterning and morphogenesis. However, previous studies in this field mainly focused on the complexes and interaction of cells and ECM. This paper pays particular attention to ECM and demonstrates that collagen, a major ECM component, natively possesses the reproducible and definite patterning ability reaching centimeter-scale length. The macroscopic pattern consists of striped transparent layers. The observation under crossed Nicols demonstrates that the layers consist of alternately arranged polarized and unpolarized parts. Confocal fluorescence microscopy studies revealed that the polarized and unpolarized segments include collagen-rich and -poor regions, respectively. The patterning process was proposed based on the Liesegang banding formation, which are mineral precipitation bands formed in hydrogel matrixes. These findings will give hints to the questions about long-distance cell alignment and provide new clues to artificially control cell placement over micron size in the field of regenerative medicine.
在内脏器官和组织中观察到的形状和图案能够在很长的距离（长达数毫米）内可重复且稳定地产生。剩下的最基本问题是这些长距离的形状和图案是如何从遗传信息中形成的。最近的研究表明，细胞外基质（ECM）作为细胞能够进行组织和通讯的结构基础起着关键作用。细胞外基质可能是理解长距离图案形成和形态发生潜在机制的关键。然而，该领域以前的研究主要集中在细胞与细胞外基质的复合物及相互作用上。本文特别关注细胞外基质，并证明胶原蛋白作为细胞外基质的主要成分，天然具有可达厘米级长度的可重复且确定的图案形成能力。宏观图案由条纹状透明层组成。在正交尼科耳棱镜下观察表明，这些层由交替排列的偏振和非偏振部分组成。共聚焦荧光显微镜研究显示，偏振和非偏振部分分别包含富含胶原蛋白和缺乏胶原蛋白的区域。图案形成过程是基于李赛根环带形成提出的，李赛根环带是在水凝胶基质中形成的矿物沉淀带。这些发现将为长距离细胞排列问题提供线索，并为再生医学领域中人工控制微米级细胞放置提供新的线索。
