title: Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy.
abstract: Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.
authors.affiliation: Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM U1182, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bancelin
authors.affiliation: Solids Mechanics Laboratory Ecole Polytechnique, CNRS, Mines ParisTech, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lynch
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, ENS-Lyon, CNRS UMR 5242, Université Lyon 1, 46 Allée d'Italie, 69364 Lyon, cedex 07 France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonod-Bidaud
authors.affiliation: Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM U1182, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ducourthial
authors.affiliation: Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM U1182, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Psilodimitrakopoulos
authors.affiliation: Centre for Mathematical Morphology, MINES ParisTech, PSL Research University, 35 rue St Honoré, 77300 Fontainebleau, France.
authors.forename: Petr
authors.initials: P
authors.lastname: Dokládal
authors.affiliation: Solids Mechanics Laboratory Ecole Polytechnique, CNRS, Mines ParisTech, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Allain
authors.affiliation: Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM U1182, 91128 Palaiseau Cedex, FRANCE.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Schanne-Klein
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, ENS-Lyon, CNRS UMR 5242, Université Lyon 1, 46 Allée d'Italie, 69364 Lyon, cedex 07 France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000648:ultrastructure; D024062:Collagen Type V / Q000235:genetics; D020405:Dermis / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000235:genetics / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods*; D017785:Photons; D012867:Skin / Q000503:physiopathology*
chemical_list: D024062:Collagen Type V; D003094:Collagen