title: Proteomic analysis of integrin-associated complexes from mesenchymal stem cells.
abstract: OBJECTIVE
  Multipotent mesenchymal stem cells (MSCs) have the capability to differentiate down adipocyte, osteocyte and chondrocyte lineages and as such offer a range of potential therapeutic applications. The composition and stiffness of the extracellular matrix (ECM) environment that surrounds cells dictates their transcriptional programme, thereby affecting stem cell lineage decision-making. Cells sense force via linkages between themselves and their microenvironment, and this is transmitted by integrin receptors and associated adhesion signalling complexes. To identify regulators of MSC force sensing, we sought to catalogue MSC integrin-associated adhesion complex composition.
  
  
  METHODS
  Adhesion complexes formed by MSCs plated on the ECM ligand fibronectin were isolated and characterised by MS. Identified proteins were interrogated by comparison to a literature-based reference set of cell adhesion-related components and using ontological and protein-protein interaction network analyses.
  
  
  RESULTS
  Adhesion complex-specific proteins in MSCs were identified that comprised predominantly cell adhesion-related adaptors and actin cytoskeleton regulators. Furthermore, LIM domain-containing proteins in MSC adhesion complexes were highlighted, which may act as force-sensing components.
  
  
  CONCLUSIONS
  These data provide a valuable resource of information regarding the molecular connections that link integrins and adhesion signalling in MSCs, and as such may present novel opportunities for therapeutic intervention.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Jila N
authors.initials: JN
authors.lastname: Ajeian
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Horton
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: Astudillo
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Byron
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Askari
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Angélique
authors.initials: A
authors.lastname: Millon-Frémillon
authors.affiliation: Biological Mass Spectrometry Core Facility, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.affiliation: North West Embryonic Stem Cell Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kimber
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Humphries
mesh_terms: D030562:Databases, Protein; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D040901:Proteomics
chemical_list: D016023:Integrins
keywords: Extracellular matrix; Integrin; LIM domain; Mechanotransduction; Mesenchymal stem cell