Proposed mechanism of lateral association of VWF. The Cys2431-Cys2453 disulfide bond in the C2 domain (shown in red) is reduced by a reductase in blood or in the injured vascular wall. The Cys2431 thiolate anion (present as a certain percentage of all thiols by action of the buffer) attacks the Cys2431 sulfur atom of the Cys2431-Cys2453 disulfide bond of another VWF molecule resulting in a disulfide-linked VWF lateral dimer. A VWF trimer may be formed when the Cys2451 thiolate anion (shown in green) of one of the VWF molecules in the dimer attacks the Cys2431 sulfur atom of the Cys2431-Cys2453 disulfide bond of a third VWF molecule. Higher-order oligomers of VWF may be formed by the addition of other molecules by the same reaction.