title: The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces.
abstract: Controlling mesenchymal stromal cell (MSC) shape is a novel method for investigating and directing MSC behaviour in vitro. it was hypothesized that specifigc MSC shapes can be generated by using stiffness-defined biomaterial surfaces and by applying cyclic tensile forces. Biomaterials used were thin and thick silicone sheets, fibronectin coating, and compacted collagen type I sheets. The MSC morphology was quantified by shape descriptors describing dimensions and membrane protrusions. Nanoscale stiffness was measured by atomic force microscopy and the expression of smooth muscle cell (SMC) marker genes (ACTA2, TAGLN, CNN1) by quantitative reverse-transcription polymerase chain reaction. Cyclic stretch was applied with 2.5% or 5% amplitudes. Attachment to biomaterials with a higher stiffness yielded more elongated MSCs with fewer membrane protrusions compared with biomaterials with a lower stiffness. For cyclic stretch, compacted collagen sheets were selected, which were associated with the most elongated MSC shape across all investigated biomaterials. As expected, cyclic stretch elongated MSCs during stretch. One hour after cessation of stretch, however, MSC shape was rounder again, suggesting loss of stretch-induced shape. Different shape descriptor values obtained by different stretch regimes correlated significantly with the expression levels of SMC marker genes. Values of approximately 0.4 for roundness and 3.4 for aspect ratio were critical for the highest expression levels of ACTA2 and CNN1. Thus, specific shape descriptor values, which can be generated using biomaterial-associated stiffness and tensile forces, can serve as a template for the induction of specific gene expression levels in MSC. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Siegfried Weller Institute for Trauma Research, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Uynuk-Ool
authors.affiliation: Siegfried Weller Institute for Trauma Research, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rothdiener
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Brandan
authors.initials: B
authors.lastname: Walters
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hegemann
authors.affiliation: Siegfried Weller Institute for Trauma Research, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Palm
authors.affiliation: Siegfried Weller Institute for Trauma Research, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Phong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: University Medical Clinic, Department II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Seeger
authors.affiliation: Clinic for Trauma and Restorative Surgery, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stöckle
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Stegemann
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Wilhelm K
authors.initials: WK
authors.lastname: Aicher
authors.affiliation: Department of Anatomy, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Kurz
authors.affiliation: Siegfried Weller Institute for Trauma Research, BG Trauma Clinic Tübingen, University of Tübingen, Tübingen, Germany.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Hart
authors.affiliation: University Medical Clinic, Department II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Klein
authors.affiliation: Department of Orthopedics and Trauma Surgery, Medical Center - Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Rolauffs
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013718:Tensile Strength; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers
keywords: MSC; aspect ratio; biomaterial; circularity; compacted collagen; cyclic stretch; mesenchymal stromal cell; myogenic differentiation; nanoscale stiffness; roundness; shape; shape descriptor; silicone; solidity