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Tuning cell adhesion geometry can affect cytoskeleton organization and the distribution of cytoskeleton forces, which play critical roles in controlling cell functions. To elucidate the geometrical relationship with cytoskeleton force distribution, it is necessary to control cell morphology. In this study, a series of dextral vortex micropatterns were prepared to precisely control cell morphology for investigating the influence of the curvature degree of adhesion curves on intracellular force distribution and stem cell differentiation at a sub-cellular level. Peripherial actin filaments of micropatterned cells were assembled along the adhesion curves and showed different orientations, filament thicknesses and densities. Focal adhesion and cytoskeleton force distribution were dependent on the curvature degree. Intracellular force distribution was also regulated by adhesion curves. The cytoskeleton and force distribution affected the osteogenic differentiation of mesenchymal stem cells through a YAP/TAZ-mediated mechanotransduction process. Thus, regulation of cell adhesion curvature, especially at cytoskeletal filament level, is critical for cell function manipulation. STATEMENT OF SIGNIFICANCE: In this study, a series of dextral micro-vortexes were prepared and used for the culture of human mesenchymal stem cells (hMSCs) to precisely control adhesive curvatures (0°, 30°, 60°, and 90°). The single MSCs on the micropatterns had the same size and shape but showed distinct focal adhesion (FA) and cytoskeleton orientations. Cellular nanomechanics were observed to be correlated with the curvature degrees, subsequently influencing nuclear morphological features. As a consequence, the localization of the mechanotransduction sensor and activator-YAP/TAZ was affected, influencing osteogenic differentiation. The results revealed the pivotal role of adhesive curvatures in the manipulation of stem cell differentiation via the machanotransduction process, which has rarely been investigated.

権利情報:

• Creative Commons BY-NC-ND Attribution-NonCommercial-NoDerivs 4.0 International
  

キーワード: Adhesion geometry, Curvature degree, Cytoskeleton force, Micropattern, Mesenchymal stem cells, Osteogenic differentiation

刊行年月日: 2024-05-09

出版者: Elsevier BV

掲載誌:

• Acta Biomaterialia (ISSN: 17427061) vol. 182 p. 81-92

研究助成金:

• Japan Society for the Promotion of Science 22K19926
• Japan Society for the Promotion of Science 21H03830
• Japan Society for the Promotion of Science 24K03289

原稿種別: 著者最終稿 (Accepted manuscript)

MDR DOI: https://doi.org/10.48505/nims.4828

公開URL: https://doi.org/10.1016/j.actbio.2024.05.017

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更新時刻: 2024-10-10 09:57:56 +0900

MDRでの公開時刻: 2026-05-09 08:39:04 +0900