Multiscale Imaging Reveals the Hierarchical Organization of Fibrillin Microfibrils

Fibrillin microfibrils are evolutionarily ancient, structurally complex extracellular polymers found in mammalian elastic tissues where they endow elastic properties, sequester growth factors and mediate cell signalling; thus, knowledge of their structure and organization is essential for a more com...

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Bibliographic Details
Published in:Journal of molecular biology 2018-10, Vol.430 (21), p.4142-4155
Main Authors: Godwin, Alan R.F., Starborg, Tobias, Smith, David J., Sherratt, Michael J., Roseman, Alan M., Baldock, Clair
Format: Article
Language:English
Subjects:
ciliary zonules
extracellular matrix
fibril electron tomography
serial block-face imaging
single-particle analysis of fibers
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Summary:Fibrillin microfibrils are evolutionarily ancient, structurally complex extracellular polymers found in mammalian elastic tissues where they endow elastic properties, sequester growth factors and mediate cell signalling; thus, knowledge of their structure and organization is essential for a more complete understanding of cell function and tissue morphogenesis. By combining multiple imaging techniques, we visualize three levels of hierarchical organization of fibrillin structure ranging from micro-scale fiber bundles in the ciliary zonule to nano-scale individual microfibrils. Serial block-face scanning electron microscopy imaging suggests that bundles of zonule fibers are bound together by circumferential wrapping fibers, which is mirrored on a shorter-length scale where individual zonule fibers are interwoven by smaller fibers. Electron tomography shows that microfibril directionality varies from highly aligned and parallel, connecting to the basement membrane, to a meshwork at the zonule fiber periphery, and microfibrils within the zonule are connected by short cross-bridges, potentially formed by fibrillin-binding proteins. Three-dimensional reconstructions of negative-stain electron microscopy images of purified microfibrils confirm that fibrillin microfibrils have hollow tubular structures with defined bead and interbead regions, similar to tissue microfibrils imaged in our tomograms. These microfibrils are highly symmetrical, with an outer ring and interwoven core in the bead and four linear prongs, each accommodating a fibrillin dimer, in the interbead region. Together these data show how a single molecular building block is organized into different levels of hierarchy from microfibrils to tissue structures spanning nano- to macro-length scales. Furthermore, the application of these combined imaging approaches has wide applicability to other tissue systems. [Display omitted] •Extracellular matrix fibrillin microfibrils assemble to form ocular ligaments.•Individual beaded fibrillin microfibrils are highly symmetric biological polymers.•Zonule fibers are composed of aligned, organized arrays of fibrillin microfibrils.•Bundles of zonule fibers are wrapped by large fibers providing structural support.•Fibrillin organization shows how a single building block constructs an elastic tissue.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2018.08.012