Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy.
Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy.
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DOI：
10.1038/srep17635
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发表时间：
2015-12-03
影响因子：
4.6
通讯作者：
Ruggiero F
中科院分区：
文献类型：
--
作者：
Bancelin S;Lynch B;Bonod-Bidaud C;Ducourthial G;Psilodimitrakopoulos S;Dokládal P;Allain JM;Schanne-Klein MC;Ruggiero F
软结缔组织，如皮肤、肌腱或角膜，由约90%的细胞外基质蛋白组成，纤维状胶原是主要成分。胶原合成减少或异常通常会导致组织力学性能缺陷，这是Elhers-Danlos综合征（cEDS）的典型形式。这种结缔组织疾病是由胶原V基因突变引起的，主要特征是皮肤过度伸展。为了研究正常和病变皮肤的微观结构与宏观力学性能的关系，我们利用多光子显微镜对离体小鼠皮肤活检组织的真皮微观结构进行了单轴力学成像和定量分析。我们使用了两种用于胶原V的转基因小鼠系：一种是含有Col5a2缺失（又称pN等位基因）的cEDS小鼠模型，另一种是在皮肤中过度表达人类COL5A1基因的转基因K14-COL5A1小鼠。我们发现，在正常皮肤中，胶原纤维不断地与拉伸对齐，产生观察到的机械应力增加。此外，两种转基因系的真皮层在牵引力作用下都表现出胶原重组的改变，这可能与微观结构的改变有关。这些发现表明，我们的多尺度方法为真皮层的生物力学提供了新的重要信息，可以扩展到所有富含胶原蛋白的软组织。
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.