Abstract
SummaryFibrillin microfibrils are indispensable structural elements of connective tissues in multicellular organisms from early metazoans to humans. They have an extensible periodic beaded organization, and support dynamic tissues such as ciliary zonules that suspend the lens. In tissues that express elastin, including blood vessels, skin and lungs, microfibrils support elastin deposition and shape the functional architecture of elastic fibres. The vital contribution of microfibrils to tissue form and function is underscored by the heritable fibrillinopathies, especially Marfan syndrome with severe elastic, ocular and skeletal tissue defects. Research since the early 1990s has advanced our knowledge of biology of microfibrils, yet understanding of their mechanical and homeostatic contributions to tissues remains far from complete. This review is a personal reflection on key insights, and puts forward the conceptual hypothesis that microfibrils are structural ‘tensometers’ that direct cells to monitor and respond to altered tissue mechanics.
Highlights
This review integrates the knowledge of fibrillin microfibrils gained over the past 25 years with recent discoveries, and draws on this framework to deliver the latest insights into the pathobiology of the fibrillinopathies including Marfan syndrome
latent TGF-b binding proteins (LTBPs) do not form beaded microfibrils, we have shown that they can assemble into branching filamentous arrays that are stabilized by transglutaminase-2 and that this multimerization process is enhanced by heparan sulphate (Troilo et al 2016)
We identified a high-affinity heparan sulphate (HS)-binding site in TB5, which is downstream from the RGD-containing TB4; together with an a5b1 integrin synergy site upstream from TB4, these regions comprise the fibrillin-1 cell adhesion region (Figure 6a) (Bax et al 2007)
Summary
Fibrillin microfibrils are indispensable structural elements of connective tissues in multicellular organisms from early metazoans to humans. They have an extensible periodic beaded organization, and support dynamic tissues such as ciliary zonules that suspend the lens. In tissues that express elastin, including blood vessels, skin and lungs, microfibrils support elastin deposition and shape the functional architecture of elastic fibres. The vital contribution of microfibrils to tissue form and function is underscored by the heritable fibrillinopathies, especially Marfan syndrome with severe elastic, ocular and skeletal tissue defects. Research since the early 1990s has advanced our knowledge of biology of microfibrils, yet understanding of their mechanical and homeostatic contributions to tissues remains far from complete. This review is a personal reflection on key insights, and puts forward the conceptual hypothesis that microfibrils are structural ‘tensometers’ that direct cells to monitor and respond to altered tissue mechanics
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