![]() ‘Multimer’ denotes both branched and unbranched polymers because the biology and physics of VWF are intertwined with the linear nature of its polymer, I prefer the more specific term ‘concatamer’ for a linear polymer. VWF multimers are organised as long linear concatamers, in which each monomer disulphide bonds tail-to-tail at its C-terminus, and head-to-head at its N-terminus, with adjacent monomers ( Fig. 1). Different domains within VWF bind clotting factor VIII, collagen, platelet glycoprotein Ib (GPIb), and integrins α IIbβ 3 and α Vβ 3 ( Fig. 1A). Von Willebrand factor (VWF) is central in haemostasis and thrombosis in the rapid flow of the arteriolar circulation. Single molecule studies on the A1-GPIb receptor-ligand bond demonstrate a specialised flex-bond that enhances resistance to the strong hydrodynamic forces experienced at sites of haemorrhage. Recent structures of A2 and single molecule measurements of A2 unfolding and cleavage by ADAMTS13 illuminate the mechanisms of VWF length regulation. Elongational forces regulate haemostasis by activating binding of the A1 domain to platelet GPIbα, and over longer time periods, regulate VWF length by unfolding of the A2 domain for cleavage by ADAMTS13. Moreover, elongational hydrodynamic forces on VWF are strongest just where needed, when bound to the vessel wall, or in elongational flow in the circulation at sites of vessel rupture or vasoconstriction in haemostasis. VWF is longest at its site of secretion, where its haemostatic function is most important. Length regulation occurs post-secretion, by hydrodynamic force-regulated unfolding of the VWF A2 domain, and its cleavage by the plasma protease ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13). Orderly assembly and storage of ultra-long concatamers in helical tubules, without crosslinking of neighboring tubules, enables unfurling during secretion without entanglement. Specialisations include a pH-regulated dimeric bouquet formed by the C-terminal half of VWF and helical assembly guided by the N-terminal half that templates inter-dimer disulphide bridges. Structural specialisations enable von Willebrand factor (VWF) to assemble during biosynthesis into helical tubules in Weibel-Palade bodies (WPB). The presented results provide insights into pore-scale mechanisms of pore-clogging induced by fines migration, which is associated with gas production in HBS, as mixed fluids flow can accompany fines detachment, fines migration, and pore-clogging near wellbores.Summary. In contrast, the gas–water interfacial tension overwhelms the drag force and the particle weight, and thereby, governs pore-clogging behaviors in mixed fluid flow conditions. The particle-level force analysis also corroborates the experimental observations, showing that the drag force primarily determined by the flow velocity plays a significant role in the fines detachment against the particle weight in the single-phase flows. In two-phase flows with mixed gas–water fluids, the presence of gas–water interfaces clearly promoted pore-clogging because the fines were readily collected at gas–water interfaces, resulting in high particle concentration at the menisci. In single-phase flows, the flow velocity had a pronounced effect on determining the fines behavior, exhibiting from no or minimal fines detachment, through fines migration with no clogging, and to fines migration accompanying pore-clogging with increasing flow velocity. ![]() One-dimensional channel experiments were carried out with sandy sediments containing non-plastic silty fines to examine effects of fluid velocity and mixed fluid flows on pore-clogging occurrence. Therefore, this study explored the fines migration induced by fluid flows and the resulting pore-clogging in porous media. However, questions as to under which circumstances and to what extent the fines migration and pore-clogging occur remain poorly resolved, particularly in association with two-phase flows. Particularly, the migration of fine sediment particles can alter the hydro-mechanical properties of sediments, and reduce long-term hydrocarbon productivity by causing local-clogging around wells. ![]() Depressurization of hydrate-bearing sediments (HBS) is inevitably accompanied with sediment transport, not only structural host sediment itself but also fine particles, which can be a significant problem in producing gases from HBS, as demonstrated in recent field-scale hydrate production tests.
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