D'Urso Mirko, Kurniawan Nicholas A
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.
Front Bioeng Biotechnol. 2020 Dec 22;8:609653. doi: 10.3389/fbioe.2020.609653. eCollection 2020.
Fibroblasts are cells present throughout the human body that are primarily responsible for the production and maintenance of the extracellular matrix (ECM) within the tissues. They have the capability to modify the mechanical properties of the ECM within the tissue and transition into myofibroblasts, a cell type that is associated with the development of fibrotic tissue through an acute increase of cell density and protein deposition. This transition from fibroblast to myofibroblast-a well-known cellular hallmark of the pathological state of tissues-and the environmental stimuli that can induce this transition have received a lot of attention, for example in the contexts of asthma and cardiac fibrosis. Recent efforts in understanding how cells sense their physical environment at the micro- and nano-scales have ushered in a new appreciation that the substrates on which the cells adhere provide not only passive influence, but also active stimulus that can affect fibroblast activation. These studies suggest that mechanical interactions at the cell-substrate interface play a key role in regulating this phenotype transition by changing the mechanical and morphological properties of the cells. Here, we briefly summarize the reported chemical and physical cues regulating fibroblast phenotype. We then argue that a better understanding of how cells mechanically interact with the substrate (mechanosensing) and how this influences cell behaviors (mechanotransduction) using well-defined platforms that decouple the physical stimuli from the chemical ones can provide a powerful tool to control the balance between physiological tissue regeneration and pathological fibrotic response.
成纤维细胞是遍布人体的细胞，主要负责组织内细胞外基质（ECM）的产生和维持。它们有能力改变组织内ECM的机械性能，并转变为肌成纤维细胞，这种细胞类型通过细胞密度和蛋白质沉积的急剧增加与纤维化组织的发展相关。从成纤维细胞到肌成纤维细胞的这种转变——一种众所周知的组织病理状态的细胞标志——以及能够诱导这种转变的环境刺激受到了广泛关注，例如在哮喘和心脏纤维化的背景下。最近在理解细胞如何在微米和纳米尺度上感知其物理环境方面所做的努力带来了一种新的认识，即细胞附着的底物不仅提供被动影响，还提供能够影响成纤维细胞激活的主动刺激。这些研究表明，细胞与底物界面处的机械相互作用通过改变细胞的机械和形态特性在调节这种表型转变中起关键作用。在这里，我们简要总结已报道的调节成纤维细胞表型的化学和物理线索。然后我们认为，使用将物理刺激与化学刺激解耦的明确定义的平台，更好地理解细胞如何与底物进行机械相互作用（机械传感）以及这如何影响细胞行为（机械转导），可以提供一个强大的工具来控制生理组织再生和病理性纤维化反应之间的平衡。
