Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy.

Stéphane Bancelin,Sotiris Psilodimitrakopoulos,Florence Ruggiero,Petr Dokládal,Christelle Bonod-Bidaud,Guillaume Ducourthial,Jean-Marc Allain,Barbara Lynch,Marie-Claire Schanne-Klein

doi:10.1038/srep17635

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.

Highlights

Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components
Connective tissues such as skin, tendon, cornea and bones are made of more than 90% of extracellular matrix (ECM) proteins, collagens being by far the predominant component[1]
Mutations in collagen V gene are responsible for the classic form of the Elhers-Danlos Syndrome which is a connective tissue heritable disorder mainly characterized by defective mechanics of skin and joints[3]

Summary

Introduction

Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress 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 Connective tissues such as skin, tendon, cornea and bones are made of more than 90% (dry weight) of extracellular matrix (ECM) proteins, collagens being by far the predominant component[1]. For further insight into the microscopic processes of complex disordered tissues such as skin, a continuous monitoring of skin microstructure during mechanical assays is required

Methods

Results

Conclusion