Length of tandem repeats in fibrin's αC region correlates with fiber extensibility

The mechanical properties of blood clots are of central importance to hemostasis, thrombosis and embolism. Fibrin fiber networks are the major structural constituent of clots, and numerous studies dating back several decades have characterized their macroscopic viscoelastic properties. The fiber-level and molecular details giving rise to these properties have not been established, however. The correlation between mechanical properties and amino acid sequence is critical for a predictive understanding of the role of genetic defects in clot pathologies. To address this issue, we have developed a nanomanipulation technique for evaluating individual fibrin fibers. It consists of a combination fluorescence/atomic force microscope system that permits viewing of fiber deformation simultaneous with quantitative strain data. Recently we and our colleagues reported on the high extensibility of individual human fibrin fibers, with extensibility (or strain at breaking) of some fibers exceeding 300%, and elastic recovery with strains of up to 180%. This places human fibrin among the most extensible protein polymers, exceeding elastin and resilin in extensibility. Here we test the hypothesis that the majority of the strain is taken up by the tandem repeat segment of the flexible αC region of fibrin. Our study focused on this portion of the protein by mechanically evaluating fibrins with varying lengths of the tandem repeat segment. Using our integrated nanomanipulation system, we stretched individual fibrin fibers made of human, mouse and chicken fibrinogen which have long, intermediate and zero length tandem repeat segments respectively. We found that extensibility correlated with the lengths of the tandem repeat segments

Microtubule Acetylation Is Required for Mechanosensation in Drosophila

At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, although prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but it is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation. Yan et al. identify the major microtubule acetylase in Drosophila and show that the enzyme and microtubule acetylation broadly control mechanosensation, but not other sensory modalities. Acetylation is required for mechanosensation by the TRP channel NOMPC, and possibly other channels, by virtue of its effects on microtubule mechanical stability and/or dynamics