Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition.
There is a dynamic relationship between physical and biochemical signals presented in the stem cell microenvironment to guide cell fate determination. Model systems that modulate cell geometry, substrate stiffness or matrix composition have proved useful in exploring how these signals influence stem cell fate. However, the interplay between these physical and biochemical cues during differentiation remains unclear. Here, we demonstrate a microengineering strategy to vary single cell geometry and the composition of adhesion ligands - on substrates that approximate the mechanical properties of soft tissues - to study adipogenesis and neurogenesis in adherent mesenchymal stem cells. Cells cultured in small circular islands show elevated expression of adipogenesis markers while cells that spread in anisotropic geometries tend to express elevated neurogenic markers. Arraying different combinations of matrix protein in a myriad of 2D and pseudo-3D geometries reveals optimal microenvironments for controlling the differentiation of stem cells to these "soft" lineages without the use of media supplements.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, IL 61801, USA.
Junmin
J
Lee
Amr A
AA
Abdeen
Douglas
D
Zhang
Kristopher A
KA
Kilian
D000180:Acrylic Resins / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects
D000180:Acrylic Resins; C016680:polyacrylamide gels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
Differentiation; Mesenchymal stem cells; Microcontact printing; Microenvironment; Polyacrylamide hydrogels