Structural and compositional diversity of fibrillin microfibrils in human tissues

Area of Science:

• Extracellular Matrix Biology
• Biochemistry
• Cell Biology

Background:

• Elastic fibers, composed of fibrillin microfibrils and elastin, provide elasticity to tissues like skin and arteries.
• Fibrillin microfibrils have diverse, tissue-specific roles, but their structural and compositional variations across organs and in culture are not well understood.

Purpose of the Study:

• To investigate whether fibrillin microfibril ultrastructure and composition differ between elastin-rich (skin) and elastin-poor (eye) organs.
• To compare fibrillin microfibrils derived from tissues versus those synthesized in cell culture.
• To identify tissue-specific and fundamental protein components of fibrillin microfibrils.

Main Methods:

• Atomic force microscopy (AFM) to analyze microfibril bead morphology and periodicity.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with novel pre-MS preparation methods to assess protein composition and proteolytic susceptibility.
• Comparative analysis of microfibrils from human skin, eye, and cultured dermal fibroblasts.

Main Results:

• Fibrillin microfibrils from the human eye exhibited different bead morphology compared to those from skin.
• Tissue- and culture-derived fibrillin microfibrils showed variations in bead morphology, periodicity, and fibrillin-1 proteolytic susceptibility, unlike invariant collagen VI microfibrils.
• Skin microfibrils were enriched in elastic fiber proteins, while eye microfibrils were enriched in basement membrane proteins. Cultured microfibrils lacked key proteins like MFAP2, MFAP4, and fibrillin-2.

Conclusions:

• Fibrillin microfibrils display significant structural and compositional diversity, which is influenced by tissue source and culture conditions.
• These variations suggest tissue-specific adaptations of fibrillin microfibrils, potentially relating to their distinct functional roles.
• The study identified fundamental and culture-dependent protein components of fibrillin microfibrils, advancing our understanding of extracellular matrix assembly.