Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy
Sci Rep. 2015-12-01; 5(1):
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Bancelin S(1), Lynch B(2), Bonod-Bidaud C(3), Ducourthial G(1), Psilodimitrakopoulos S(1), Dokládal P(4), Allain JM(2), Schanne-Klein MC(1), Ruggiero F(3).
(1)Laboratory for Optics and Biosciences, Ecole Polytechnique, CNRS, INSERM U1182, 91128 Palaiseau Cedex, FRANCE.
(2)Solids Mechanics Laboratory Ecole Polytechnique, CNRS, Mines ParisTech, 91128 Palaiseau Cedex, FRANCE.
(3)Institut de Génomique Fonctionnelle de Lyon, ENS-Lyon, CNRS UMR 5242, Université Lyon 1, 46 Allée d’Italie, 69364 Lyon, cedex 07 France.
(4)Centre for Mathematical Morphology, MINES ParisTech, PSL Research University, 35 rue St Honoré, 77300 Fontainebleau, France.
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.