title: Controlling cell geometry on substrates of variable stiffness can tune the degree of osteogenesis in human mesenchymal stem cells.
abstract: The physical properties of the extracellular matrix (ECM) play an important role in regulating tissue-specific human mesenchymal stem cell (MSC) differentiation. Protein-coated hydrogels with tunable stiffness have been shown to influence lineage specific gene expression in MSCs. In addition, the control of cell shape - either through changing substrate stiffness or restricting spreading with micropatterning - has proved to be important in guiding the differentiation of MSCs. However, few studies have explored the interplay between these physical cues during MSC lineage specification. Here, we demonstrate geometric control of osteogenesis in MSCs cultured on micropatterned polyacrylamide gels. Cells cultured on fibronectin-coated gels express markers associated with osteogenesis in a stiffness dependent fashion with a maximum at ~30kPa. Controlling the geometry of single cells across the substrate demonstrates elevated osteogenesis when cells are confined to shapes that promote increased cytoskeletal tension. Patterning MSCs across hydrogels of variable stiffness will enable the exploration of the interplay between these physical cues and their relationship with the mechanochemical signals that guide stem cell fate decisions.
authors.affiliation: Department of Materials Science and Engineering, Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Junmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Amr A
authors.initials: AA
authors.lastname: Abdeen
authors.affiliation: Department of Materials Science and Engineering, Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Materials Science and Engineering, Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: kakilian@illinois.edu.
authors.forename: Kristopher A
authors.initials: KA
authors.lastname: Kilian
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D019070:Cell Lineage / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D016326:Extracellular Matrix Proteins; D020100:Hydrogels; D000099166:Polyacrylamides
keywords: Microcontact printing; Microenvironment; Polyacrylamide hydrogels; Stem cell differentiation; Substrate stiffness