title: Cardiomyocyte progenitor cell mechanoresponse unrevealed: strain avoidance and mechanosome development.
abstract: For emerging cardiac regeneration strategies, it is essential to know if and how cardiac stem cells sense and respond to the mechanical stimuli provided by their environment in the beating heart. Here, we study the response to cyclic strain of undifferentiated and predifferentiated human cardiomyocyte progenitor cells (CMPCs), as well as the formation and activation of the cellular structures involved in mechanosensing, that we termed 'mechanosome'. Once verified that the applied uniaxial cyclic strain (10%, 0.5 Hz) did not alter the cardiac lineage commitment and differentiation state of CMPCs, the cellular mechanoresponse to the applied strain was quantified by cellular orientation. While undifferentiated cells maintained their original (random) orientation, upon early cardiomyogenic differentiation (predifferentiated) CMPCs exhibited a distinct strain avoidance response after 48 h of cyclic straining. Interestingly, the mechanosome development and the activation of the mechanotransduction pathways also occurred with early cardiac differentiation of the CMPCs, regardless of the substrate or the applied cyclic strain. These results indicate that the mechanoresponse of CMPCs depends on the presence of a developed mechanosome, which only develops during early cardiomyogenic differentiation Our findings provide the first understanding of mechanotransduction in human CMPCs and as such can contribute to the improvement of cardiac regeneration strategies.
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO box 513, Groene Loper, Building 15, Gem-Zuid 4.117, 5600 MB Eindhoven, The Netherlands. c.v.c.bouten@tue.nl and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Arianna
authors.identifier: 0000-0002-3367-607X
authors.initials: A
authors.lastname: Mauretti
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO box 513, Groene Loper, Building 15, Gem-Zuid 4.117, 5600 MB Eindhoven, The Netherlands. c.v.c.bouten@tue.nl and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Noortje A M
authors.initials: NA
authors.lastname: Bax
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO box 513, Groene Loper, Building 15, Gem-Zuid 4.117, 5600 MB Eindhoven, The Netherlands. c.v.c.bouten@tue.nl and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Mieke H
authors.initials: MH
authors.lastname: van Marion
authors.affiliation: Department of Molecular Cell Biology and Center for Biomedical Genetics, Leiden University Medical Center, The Netherlands.
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO box 513, Groene Loper, Building 15, Gem-Zuid 4.117, 5600 MB Eindhoven, The Netherlands. c.v.c.bouten@tue.nl and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sahlgren
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, PO box 513, Groene Loper, Building 15, Gem-Zuid 4.117, 5600 MB Eindhoven, The Netherlands. c.v.c.bouten@tue.nl and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Carlijn V C
authors.initials: CV
authors.lastname: Bouten
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D016764:Cell Polarity; D002478:Cells, Cultured; D055119:Elastic Modulus / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013314:Stress, Mechanical