Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
ACS Appl Mater Interfaces. 2021 Nov 24;13(46):54840-54849. doi: 10.1021/acsami.1c18722. Epub 2021 Nov 10.
An understanding of cellular mechanoresponses to well-defined synthetic topographic features is crucial for the fundamental research and biomedical applications of stem cells. Structured biointerfaces, in particular the ones with nanometer and/or micrometer surficial features, have drawn more attention in the past few decades. However, it is still difficult to integrate nanostructures and microstructures onto the synthesized biointerfaces to mimic the hierarchical architecture of the native extracellular matrix (ECM). Herein, a series of "raspberry"-like hierarchical surfaces with well-defined nanofeatures and tunable nano/microfeatures have been achieved via a catecholic polymer coating technique. Cellular responses to these hierarchical interfaces were systemically studied, indicating that the nanofeatures on the raspberry surfaces significantly enhanced the mechanosensing of human mesenchymal stem cells (hMSCs) to interfacial physical cues. Cell mechanotransduction was further investigated by analyzing focal adhesion assembling, cytoskeleton organization, cell nuclear mechanics, and transcriptional activity. The results suggest that nanosize surficial features could increase cellular mechanosensing to environment physical cues. The mechanotransduction and cell fate specification were greatly enhanced by the ECM mimicking nano/microhierarchical biointerfaces but the features should be in an optimized size.
理解细胞对明确定义的合成形貌特征的机械响应对于干细胞的基础研究和生物医学应用至关重要。结构生物界面，特别是具有纳米和/或微米表面特征的生物界面，在过去几十年中受到了更多关注。然而，仍然难以将纳米结构和微结构集成到合成的生物界面上，以模拟天然细胞外基质 (ECM) 的层次结构。在此，通过儿茶酚聚合物涂覆技术，实现了一系列具有明确定义的纳米特征和可调纳米/微特征的“树莓”状分层表面。系统研究了细胞对这些分层界面的反应，表明树莓表面上的纳米特征显著增强了人间充质干细胞 (hMSC) 对界面物理线索的机械感知。通过分析黏附斑组装、细胞骨架组织、细胞核力学和转录活性进一步研究了细胞力学转导。结果表明，纳米级表面特征可以增加细胞对环境物理线索的机械感知。通过模仿 ECM 的纳米/微分层生物界面极大地增强了力学转导和细胞命运特化，但特征尺寸应优化。
