Abstract FR:

Skin is a complex organ consisting of three main layers, namely the epidermis, dermis and hypodermis. The dermis is responsible for most of the complex mechanical properties of skin, including non-linearity, anisotropy and viscoelasticity. Like all soft collagenous tissues, the dermis is constituted mostly of extracellular matrix proteins, fibrillar collagens being the major structural components. Modelling efforts using a scaling-up approach for skin generally lack appropriate micro-mechanical experiments to clarify the link between macroscopic mechanical properties and microstructural behaviour. The goal of this research was to measure the evolution of skin's microstructure during mechanical stimulation to identify the relevant mechanisms at the microscopic scale. Uniaxial tensile tests were carried out on ex vivo mice skin under a multiphoton microscope with Second Harmonic Generation detection. This technique allows for specific imaging of collagen fibres in the depth of the dermis. We were then able to simultaneously monitor the tissue's mechanical response and image the microstructural reorganisation of the fibrillar collagen network, using quantitative characterisations at both scales. We showed that the collagen fibres continuously align in the direction of traction with stretch, generating the observed mechanical response. A general framework of hypothetical microstructural mechanisms was proposed to account for the features observed experimentally. Genetic mutations inducing a decreased or abnormal collagen synthesis can result in defective mechanical properties in skin. For instance, patients suffering from Ehlers-Danlos syndrome, a general collagenous tissue disorder caused by mutations in the genes coding for a minor form of collagen, typically present hyperelastic skin. We applied our multiscale approach to two genetically-modified mice strains created in the context of investigating the Ehlers-Danlos syndrome. The ageing process is also a factor of change in skin's mechanical properties, and was investigated in this work through experiments on aged mice skin. Genetically-modified and aged mice skin exhibited altered collagen reorganisation and mechanical response during a tensile test. The variations were interpreted in the context of the microstructural interpretation developed for control mice, and can be used for phenotyping. These findings show that our multiscale approach provides new crucial information on the biomechanics of skin. It can be generalised to study other pathologies, other collagenous tissues, or other mechanical properties, such as the biaxial or viscoelastic response.