Thickness sensing of hMSCs on collagen gel directs stem cell fate.
Mechanically compliant substrate provides crucial biomechanical cues for multipotent stem cells to regulate cellular fates such as differentiation, proliferation and maintenance of their phenotype. Effective modulus of which cells sense is not only determined by intrinsic mechanical properties of the substrate, but also the thickness of substrate. From our study, it was found that interference from underlying rigid support at hundreds of microns away could induce significant cellular response. Human mesenchymal stem cells (hMSCs) were cultured on compliant biological gel, collagen type I, of different thickness but identical ECM composition and local stiffness. The cells sensed the thin gel (130 μm) as having a higher effective modulus than the thick gel (1440 μm) and this was reflected in their changes in morphology, actin fibers structure, proliferation and tissue specific gene expression. Commitment into neuronal lineage was observed on the thin gel only. Conversely, the thick gel (1440 μm) was found to act like a substrate with lower effective modulus that inhibited actin fiber polymerization. Stem cells on the thick substrate did not express tissue specific genes and remained at their quiescent state. This study highlighted the need to consider not only the local modulus but also the thickness of biopolymer gel coating during modulation of cellular responses.
Leong
Wen Shing
WS
Division of Materials Technology, Nanyang Technological University, School of Materials Science and Engineering, 50 Nanyang Avenue, Singapore 639798, Singapore.
Tay
Chor Yong
CY
Yu
Haiyang
H
Li
Ang
A
Wu
Shu Cheng
SC
Duc
Duong-Hong
DH
Lim
Chwee Teck
CT
Tan
Lay Poh
LP
D000199:Actins / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D055119:Elastic Modulus; D005782:Gels; D015870:Gene Expression; D006801:Humans; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology
D000199:Actins; D024042:Collagen Type I; D005782:Gels