Department of Biomedical Engineering-FB40, University of Groningen, University Medical Center Groningen, Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Biomater Sci. 2020 May 7;8(9):2638-2652. doi: 10.1039/d0bm00264j. Epub 2020 Apr 5.
Topography-driven alterations in cell morphology tremendously influence cell biological processes, particularly stem cell differentiation. Aligned topography is known to alter the cell shape, which we anticipated to also induce altered physical properties of the cell. Here, we show that topography has a significant influence on single cell stiffness of human bone marrow derived-Mesenchymal Stem Cells (hBM-MSCs) and the osteogenic differentiation of these. Aligned topographies were used to control the cell elongation, depicted as the cell aspect ratio (C). Intriguingly, an equal C elicited from different topographies, resulted in highly altered differentiation behavior and the underlying single cell mechanics was found to be critical. The cell behavior was found to be focal adhesion-mediated and induced stiffness alterations rather than just influencing the cell elongation. The effect was further corroborated by investigations of the transcriptional regulators YAP. Our study provides insight into how mechanical properties of the cell, which are stimulated by topography, modulate the osteogenesis of hBM-MSCs, which is beneficial for improving the understanding of interactions between stem cells and topography for developing applications of tissue engineering and regenerative medicine.
地形驱动的细胞形态改变极大地影响细胞的生物学过程，特别是干细胞分化。众所周知，取向地形会改变细胞的形状，我们预计这也会引起细胞物理性质的改变。在这里，我们表明地形对人骨髓间充质干细胞（hBM-MSCs）的单细胞硬度及其成骨分化有显著影响。使用取向的地形来控制细胞的伸长，表现为细胞纵横比（C）。有趣的是，来自不同地形的相等 C 导致高度改变的分化行为，并且发现底层单细胞力学是关键。细胞行为被发现是由粘着斑介导的，并且诱导了刚度的改变，而不仅仅是影响细胞的伸长。通过对转录调节因子 YAP 的研究进一步证实了这一效应。我们的研究深入了解了细胞的力学特性是如何被地形刺激的，从而调节 hBM-MSCs 的成骨作用，这有助于提高对干细胞与地形相互作用的理解，以开发组织工程和再生医学的应用。
