title: Cell contractility arising from topography and shear flow determines human mesenchymal stem cell fate.
abstract: Extracellular matrix (ECM) of the human Mesenchymal Stem Cells (MSCs) influences intracellular tension and is known to regulate stem cell fate. However, little is known about the physiological conditions in the bone marrow, where external forces such as fluid shear stress, apart from the physical characteristics of the ECM, influence stem cell response. Here, we hypothesize that substrate topography and fluid shear stress alter the cellular contractile forces, influence the genetic expression of the stem cells and hence alter their lineage. When fluid shear stress was applied, human MSCs with higher contractility (seeded on 1 μm wells) underwent osteogenesis, whereas those with lower contractility (seeded on 2 μm gratings) remained multipotent. Compared to human MSCs seeded on gratings, those seeded on wells exhibited altered alignment and an increase in the area and number of focal adhesions. When actomyosin contractility was inhibited, human MSCs did not exhibit differentiation, regardless of the topographical feature they were being cultured on. We conclude that the stresses generated by the applied fluid flow impinge on cell contractility to drive the stem cell differentiation via the contractility of the stem cells.
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.|Department of Biomedical Engineering, National University of Singapore, 117583, Singapore.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Sonam
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.
authors.forename: Sharvari R
authors.initials: SR
authors.lastname: Sathe
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.|Department of Biomedical Engineering, National University of Singapore, 117583, Singapore.|Department of Surgery, National University of Singapore, 119228, Singapore.
authors.forename: Evelyn K F
authors.initials: EK
authors.lastname: Yim
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.|Department of Biological Sciences, Columbia University, New York, 10027, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
authors.affiliation: Mechanobiology Institute, National University of Singapore, 117411, Singapore.|Department of Biomedical Engineering, National University of Singapore, 117583, Singapore.|Department of Mechanical Engineering, National University of Singapore, 117575, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D055592:Biophysical Phenomena; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis; D015363:Quinolones / Q000494:pharmacology; D013314:Stress, Mechanical; D013450:Sulfones / Q000494:pharmacology
chemical_list: C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; D015363:Quinolones; D013450:Sulfones; D000205:Actomyosin