title: Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation.
abstract: Both chemical and mechanical stimuli can dramatically influence cell behavior. By optimizing the signals cells experience, it may be possible to control the behavior of therapeutic cell populations. In this work, biomimetic geometries of adhesive ligands, which recapitulate the morphology of mature cells, are used to direct human mesenchymal stem cell (HMSC) differentiation toward a desired lineage. Specifically, adipocytes cultured in 2D are imaged and used to develop biomimetic virtual masks used in laser scanning lithography to form patterned fibronectin surfaces. The impact of adipocyte-derived pattern geometry on HMSC differentiation is compared to the behavior of HMSCs cultured on square and circle geometries, as well as adipocyte-derived patterns modified to include high stress regions. HMSCs on adipocyte mimetic geometries demonstrate greater adipogenesis than HMSCs on the other patterns. Greater than 45% of all HMSCs cultured on adipocyte mimetic patterns underwent adipogenesis as compared to approximately 19% of cells on modified adipocyte patterns with higher stress regions. These results are attributed to variations in cytoskeletal tension experienced by cells on the different protein micropatterns. The effects of geometry on adipogenesis are mitigated by the incorporation of a cytoskeletal protein inhibitor; exposure to this inhibitor leads to increased adipogenesis on all patterns examined.
authors.affiliation: School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University , Providence, Rhode Island 02912, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Shukla
authors.affiliation: Department of Biomedical Engineering, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Slater
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine , Houston, Texas 77030, United States.
authors.forename: James C
authors.initials: JC
authors.lastname: Culver
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine , Houston, Texas 77030, United States.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.affiliation: Department of Biomedical Engineering, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
mesh_terms: D017667:Adipocytes; D032701:Biomimetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells
keywords: adipogenesis; biomimetic; laser scanning lithography; micropatterns; stem cell engineering