Tripeptide Arg-Gly-Asp (RGD) modifies the molecular mechanical properties of the non-muscle myosin IIA in human bone marrow-derived myofibroblasts seeded in a collagen scaffold

Autoři: Yves Lecarpentier aff001;  Vincent Kindler aff002;  Marie-Luce Bochaton-Piallat aff003;  Antonija Sakic aff003;  Victor Claes aff004;  Jean-Louis Hébert aff005;  Alexandre Vallée aff006;  Olivier Schussler aff008
Působiště autorů: Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien, Meaux, France aff001;  Department of Specialties in Medicine, Hematology Service, Geneva University Hospital, Switzerland Faculty of Medicine, Geneva, Switzerland aff002;  Department of Pathology and Immunology, Centre Médical Universitaire Geneva, Faculty of Medicine, Geneva, Switzerland aff003;  Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Belgium aff004;  Institut de Cardiologie, Hôpital de la Pitié-Salpétrière, Paris, France aff005;  Paris-Descartes University, Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Hôtel-Dieu Hospital, Paris, France aff006;  DRCI (Délégation à la Recherche Clinique et Industrielle) Hôpital Foch, Suresnes, France aff007;  Department of Cardiovascular Surgery, Research Laboratory, Geneva University Hospitals, Geneva, Switzerland aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Mesenchymal stem cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate in order to generate myofibroblasts. When MSCs were seeded in solid collagen scaffolds, they differentiated into myofibroblasts that were observed to strongly bind to the substrate, forming a 3D cell scaffold network that developed tension and shortening after KCl stimulation. Moreover, MSC-laden scaffolds recapitulated the Frank-Starling mechanism so that active tension increased in response to increases in the initial length of the contractile system. This constituted a bioengineering tissue that exhibited the contractile properties observed in both striated and smooth muscles. By using the A. F. Huxley formalism, we determined the myosin crossbridge (CB) kinetics of attachment (f1) and detachment (g1 and g2), maximum myosin ATPase activity, molar myosin concentration, unitary CB force and maximum CB efficiency. CB kinetics were dramatically slow, characterizing the non-muscle myosin type IIA (NMMIIA) present in myofibroblasts. When MSCs were seeded in solid collagen scaffolds functionalized with Arg-Gly-Asp (RGD), contractility increased and CB kinetics were modified, whereas the unitary NMMIIA-CB force and maximum CB efficiency did not change. In conclusion, we provided a non-muscle bioengineering tissue whose molecular mechanical characteristics of NMMIIA were very close to those of a non-muscle contractile tissue such as the human placenta.

Klíčová slova:

Adenosine triphosphatase – Collagens – Fibroblasts – Mechanical properties – Mesenchymal stem cells – Muscle contraction – Myosins – Mechanical tension


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