title: Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation.
abstract: Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well-defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward-lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin-A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell-instructive material parameter in the field of biomaterial-guided tissue regeneration.
authors.affiliation: Julius Wolff Institute Charité-Universitätsmedizin Berlin Augustenburger Platz 1D-13353 Berlin Germany; Department of Biomaterials Science and Technology Twente University P.O. Box 2177500 AE Enschede The Netherlands; Department of Biomedical Engineering Eindhoven University of Technology P.O. Box 5135600 MB Eindhoven The Netherlands.
authors.forename: Maike
authors.initials: M
authors.lastname: Werner
authors.affiliation: Department of Biomaterials Science and Technology Twente University P.O. Box 217 7500 AE Enschede The Netherlands.
authors.forename: Sébastien B G
authors.initials: SB
authors.lastname: Blanquer
authors.affiliation: Department of Biomaterials Science and Technology Twente University P.O. Box 2177500 AE Enschede The Netherlands; Department of Oral and Maxillofacial Diseases University of Helsinki Haartmaninkatu 8FI00014 Helsinki Finland.
authors.forename: Suvi P
authors.initials: SP
authors.lastname: Haimi
authors.affiliation: Julius Wolff Institute Charité-Universitätsmedizin Berlin Augustenburger Platz 1 D-13353 Berlin Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Korus
authors.affiliation: Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1 14476 Potsdam Germany.
authors.forename: John W C
authors.initials: JW
authors.lastname: Dunlop
authors.affiliation: Julius Wolff Institute Charité-Universitätsmedizin Berlin Augustenburger Platz 1D-13353 Berlin Germany; Berlin-Brandenburg Center for Regenerative Therapies Charité-Universitätsmedizin Berlin Augustenburger Platz 1D-13353 Berlin Germany.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Department of Biomaterials Science and Technology Twente University P.O. Box 2177500 AE Enschede The Netherlands; Department of Biomedical Engineering University Medical Centre Groningen University of Groningen Antonius Deusinglaan 19713 AV Groningen The Netherlands.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Grijpma
authors.affiliation: Julius Wolff Institute Charité-Universitätsmedizin Berlin Augustenburger Platz 1D-13353 Berlin Germany; Berlin-Brandenburg Center for Regenerative Therapies Charité-Universitätsmedizin Berlin Augustenburger Platz 1D-13353 Berlin Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Petersen
keywords: 3D surface curvature; cell migration; nuclear mechanics; osteogenic differentiation; stereolithography