Fibrillin Microfibrils: A Key Role for the Interbead Region in Elasticity

Fibrillin microfibrils have essential roles in elastic fiber formation and elastic tissue homeostasis, as well as transforming growth factor-β sequestration. A role for fibrillin microfibrils in tissue elasticity has been implied by their ability to increase periodicity from 56 to 150 nm. In this study, we found that microfibril periodicity and structure are dependent on the ionic strength of the buffer and Ca2+ concentration; we then used these properties of the microfibril to trap conformation intermediates. Transmission electron microscopy imaging of microfibrils with a range of periodicities between 56 and 154 nm revealed a gross conformational change in the interbead region that accommodates the length change. At periodicities below 85 nm, four thin filaments are visualized in the interbead region, but at periodicities greater than 85 nm, two thick filaments are seen. The diameter of the bead remains almost constant at all periodicities, but there is a decrease in stain-exclusion above 85 nm periodicity, which is likely to correspond to a decrease in bead mass. Additionally, we identified eight molecules in cross-section through a microfibril, allowing us to understand microfibril organization in three dimensions. In conclusion, when microfibrils extend, there is a large molecular rearrangement within the interbead region, and this highlights a possible role for Ca2+ in stabilizing the microfibril architecture and moderating extension in vivo.