title: Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase and RhoA kinase sensors.
abstract: The study of mesenchymal stem cell (MSC) migration under flow conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcome in stem-cell-based cell therapy and regenerative medicine. We used peer-reviewed open source software to develop methods for efficiently and accurately tracking, measuring and processing cell migration as well as morphology. Using these tools, we investigated MSC migration under flow-induced shear and tested the molecular mechanism with stable knockdown of focal adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated following the flow direction in a shear stress magnitude-dependent manner, as assessed by root mean square displacement and mean square displacement, motility coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology adaptation capability and reduced cellular motility for both static and flow conditions. Interestingly, ROCK silencing significantly increased migration tendency especially under flow. Blocking ROCK, which is known to reduce cytoskeletal tension, may lower the resistance to skeletal remodelling during the flow-induced migration. Our data thus propose a potentially differential role of focal adhesion and cytoskeletal tension signalling elements in MSC migration under flow shear.
authors.affiliation: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Riehl
authors.affiliation: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Jeong Soon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Ligyeom
authors.initials: L
authors.lastname: Ha
authors.affiliation: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA The Graduate School of Dentistry, Kyung Hee University, Seoul, Korea jlim4@unl.edu.
authors.forename: Jung Yul
authors.initials: JY
authors.lastname: Lim
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D019295:Computational Biology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D020868:Gene Silencing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D044968:Regenerative Medicine; D033081:Shear Strength; D015398:Signal Transduction; D012984:Software; D013314:Stress, Mechanical; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D054460:rho-Associated Kinases
keywords: RhoA kinase; fluid shear; focal adhesion kinase; stem cell migration; time lapse