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 (CAR). Intriguingly, an equal CAR 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.

中文翻译：

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地形引起的干细胞硬度变化影响成骨分化。

细胞形态的地形驱动改变极大地影响了细胞生物学过程，特别是干细胞分化。已知对齐的形貌会改变细胞的形状，我们预计这也会引起细胞物理特性的改变。在这里，我们显示地形对人骨髓源性间充质干细胞（hBM-MSC）的单细胞硬度及其成骨分化有重大影响。对准的形貌用于控制细胞伸长，描绘为细胞长宽比（CAR）。有趣的是，从不同的地形中得出的均等CAR导致分化行为发生了很大变化，并且发现基本的单细胞机制至关重要。发现细胞行为是局灶性粘附介导的和诱导的刚度改变，而不仅仅是影响细胞伸长。通过对转录调节子YAP的研究进一步证实了该作用。我们的研究提供了关于拓扑学刺激的细胞机械特性如何调节hBM-MSC的成骨作用的见解，这有助于增进对干细胞与拓扑学之间相互作用的理解，从而开发组织工程和再生医学的应用。