title: Endothelial basement membrane laminin 511 is essential for shear stress response.
abstract: Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1-positive/vinculin-positive focal adhesions, and reduced junctional association of actin-myosin II In vitro assays reveal that β1 integrin-mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE-cadherin, stabilizing it at cell junctions and increasing cell-cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Jacopo
authors.identifier: 0000-0001-6731-9612
authors.initials: J
authors.lastname: Di Russo
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Anna-Liisa
authors.identifier: 0000-0003-0389-5850
authors.initials: AL
authors.lastname: Luik
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Lema
authors.initials: L
authors.lastname: Yousif
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Sigmund
authors.initials: S
authors.lastname: Budny
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.|Institute of Physiology II, University of Muenster, Muenster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.|Institute of Physiology II, University of Muenster, Muenster, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Hofschröer
authors.affiliation: Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.|Institute of Medical Physics, University of Muenster, Muenster, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Klingauf
authors.affiliation: Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: van Bavel
authors.affiliation: Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Erik Ntp
authors.initials: EN
authors.lastname: Bakker
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hellstrand
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhattachariya
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.affiliation: Laboratoire de Physique Statistique, École Normale Superieure - PSL Research University, Paris, France.|CNRS UMR8550, Sorbonne Universités - UPMC Univ Paris 06, Université Paris, Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Pincet
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Hallmann
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany sorokin@uni-muenster.de.|Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany.
authors.forename: Lydia M
authors.identifier: 0000-0001-7704-7921
authors.initials: LM
authors.lastname: Sorokin
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013314:Stress, Mechanical; D013312:Stress, Physiological
chemical_list: D007797:Laminin; C119013:laminin 10
keywords: VE‐cadherin; endothelial cells; focal adhesions; laminin 511; shear stress