Figure 2. Assembly of VWF strands depends on vessel diameter and turns.
(a,b) Secreted VWF from the activated endothelium formed strands along the direction of flow on a single straight vessel with a diameter of 500 μm (b. zoomed-in view of A, showing neighbouring parallel VWF fibres assembled to thicker strands). (c,d) Secreted VWF near the luminal wall of a vessel with diameter of 150 μm, (c) multiple strands from one or two cells converged to one thicker strand and (d) VWF strands follow the major direction of flow, but show some deviation due to surface irregularities. (e) VWF strands follow vessel turns, changing directions and remaining bound to the vessel wall in a 500-μm diameter vessel. (f) VWF strands remain bound to the vessel wall in a tortuous vessel with a diameter of 500 μm. Arrowheads: individual VWF strands self-associated into thicker strands in regions of high shear stress; asterisks: regions of low shear stress lack VWF strands; green: VWF, blue: nuclei. The upper left corner of the panel shows the COMSOL simulation of flow streamlines (white lines) and shear rate colour map at the cross-sectional plane with a distance to the bottom wall of 5% of the vessel diameter. (g) z-stack projection and cross-sectional view of confocal image of VWF transluminal bundles through microvessels of diameter <200 μm. (h) z-section projection of confocal images of g near the top wall (I: z >95 μm), vessel centre (J: 35 μm <z <75 μm) and the bottom wall (K: z <25 μm). Red: CD31, green: VWF and blue: nuclei. Asterisks: anchoring points of VWF fibres at the inner corners of vessel turns; arrowhead: self-association and thickening of VWF strands. (l) COMSOL simulation of flow through tortuous vessels showing the colour-coded flow speed at the centre longitudinal plane (top panel), shear rate at transverse cross-sections before and after the vessel turns (middle panel) and z-direction velocity at corresponding planes (bottom panel). (m) A continuous VWF strand of ∼5 cm in length (in green) extending through a torturous vessel along the shortest flow path. N >6.
