Fell‐Muir Lecture: Fibrillin microfibrils: structural tensometers of elastic tissues?

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.