(NVKP-16-1-2016-0017 National Heart Program) Támogató: NKFIH
(2020-1.1.6-JOVO-2021-00013)
(2020-4.1.1.-TKP2020)
(TKP2021-NVA-15)
(TKP2021-EGA-23) Támogató: Innovációs és Technológiai Minisztérium
(TKP2021-NVA)
(TKP2021-EGA)
(RRF-2.3.1-21-2022-00003)
Von Willebrand factor (VWF) is a multimer with a variable number of protomers, each
of which is a head-to-head dimer of two multi-domain monomers. VWF responds to shear
through the unfolding and extension of distinct domains, thereby mediating platelet
adhesion and aggregation to the injured blood vessel wall. VWF's C1-6 segment uncoils
and then the A2 domain unfolds and extends in a hierarchical and sequential manner.
However, it is unclear whether there is any reservoir of further extensibility. Here,
we explored the presence of cryptic extensibility in VWF by nanodissecting individual,
pre-stretched multimers with atomic force microscopy (AFM). The AFM cantilever tip
was pressed into the surface and moved in a direction perpendicular to the VWF axis.
It was possible to pull out protein loops from VWF, which resulted in a mean contour
length gain of 217 nm. In some cases, the loop became cleaved, and a gap was present
along the contour. Frequently, small nodules appeared in the loops, indicating that
parts of the nanodissected VWF segment remained folded. After analyzing the nodal
structure, we conclude that the cryptic extensibility lies within the C1-6 and A1-3
regions. Cryptic extensibility may play a role in maintaining VWF’s functionality
in extreme shear conditions.