Journal
ADVANCED MATERIALS
Volume 31, Issue 16, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201900582
Keywords
cellular mechanics; lineage diversification; matrix chirality
Categories
Funding
- National Key R&D Program of China [2018YFC1105301, 2018YFC1105302, 2018YFC1105303, 2018YFC1105304, 2017YFC1104302]
- National Natural Science Foundation of China [81425007, 31570990, 51833006, 51772006, 31670993, 21425314]
- Fok Ying Tong Education Foundation [151034]
- Innovation Program of Shanghai Municipal Education Commission [201701070002E00061]
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Biogenesis and tissue development are based on the heterogenesis of multipotent stem cells. However, the underlying mechanisms of stem cell fate specification are unclear. Chirality is one of the most crucial factors that affects stem cell development and is implicated in asymmetrical cell morphology formation; however, its function in heterogeneous cell fate determination remains elusive. In this study, it is reported that the chirality of a constructed 3D extracellular matrix (ECM) differentiates mesenchymal stem cells to diverse lineages of osteogenic and adipogenic cells by providing primary heterogeneity. Molecular analysis shows that left-handed chirality of the ECM enhances the clustering of the mechanosensor Itg alpha 5, while right-handed chirality decreases this effect. These differential adhesion patterns further activate distinct mechanotransduction events involving the contractile state, focal adhesion kinase/extracellular signal-regulated kinase 1/2 cascades, and yes-associated protein/runt-related transcription factor 2 nuclear translocation, which direct heterogeneous differentiation. Moreover, theoretical modeling demonstrates that diverse chirality mechanosensing is initiated by biphasic modes of fibronectin tethering. The findings of chirality-dependent lineage specification of stem cells provide potential strategies for the biogenesis of organisms and regenerative therapies.
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