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Peer-reviewedCC BYResearch and Practice in Thrombosis and Haemostasis

Von Willebrand factor A2 domain inhibits A1-DNA binding while preserving A1-platelet interaction under flow: evidence from recombinant domain constructs

  • Zhitong Peng1
  • Xiaoxi Sun2
  • Guangzhou Qu3
  • Jinhua Fang2
  • Aiying Liu1
  • Yuming Huang4
  • Zhiwei Wu1
  • Junxian Yang5
  • Jie Ma3
  • Jiangguo Lin6
6 affiliations
  1. 1School of Medicine, South China University of Technology, Guangzhou, People's Republic of China
  2. 2Department of Medical Research, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China
  3. 3School of Physics, Sun Yat-sen University, Guangzhou, People's Republic of China; State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou, People's Republic of China
  4. 4School of Basic Medical Sciences, Southern Medical University, Guangzho
  5. 5School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People's Republic of China
  6. 6School of Medicine, South China University of Technology, Guangzhou, People's Republic of China; Department of Medical Research, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China
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Abstract

Background: Circulating cell-free DNA levels increase in the circulation during inflammation and thrombosis. During immunothrombosis, neutrophil extracellular traps provide long DNA fibers with prothrombotic properties. Von Willebrand factor (VWF) has been reported to interact with DNA via its A1 domain; however, the consequences of this interaction and its regulation by the adjacent A2 domain remain poorly understood. Objectives: Using recombinant VWF domain constructs, we aimed to characterize VWF-A1–DNA interactions and to determine whether the VWF-A2 domain modulates A1–DNA binding and its impact on platelet adhesion under flow. Methods: VWF-A1–DNA interactions were examined using atomic force microscopy, magnetic tweezers, ELISAs, and microfluidic flow assays. Both recombinant A1 and mammalian-expressed A1A2 constructs were employed to assess physiological relevance. Results: VWF-A1 bound to DNA and induced concentration–dependent DNA compaction. DNA binding to VWF-A1 significantly impaired platelet adhesion under flow conditions. In contrast, the A2 domain inhibited VWF-A1–DNA binding, as shown using both isolated A2 and A1A2 constructs, and mitigated DNA’s inhibitory effect on A1-mediated platelet adhesion. Conclusion: These findings suggest that, within recombinant VWF domain constructs, VWF-A1 compacts DNA and that the A2 domain negatively regulates A1–DNA interactions while preserving A1-mediated platelet binding under flow. Although further validation in native multimeric VWF and physiologically relevant models is required, these results provide new insights into how the A2 domain differentially regulates VWF-A1 interactions with DNA and platelets.

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Cite

BibTeXRIS
BibTeX
@article{peng2026willebrand,
  title = {{Von Willebrand factor A2 domain inhibits A1-DNA binding while preserving A1-platelet interaction under flow: evidence from recombinant domain constructs}},
  author = {Zhitong Peng and Xiaoxi Sun and Guangzhou Qu and Jinhua Fang and Aiying Liu and Yuming Huang and Zhiwei Wu and Junxian Yang and Jie Ma and Jiangguo Lin},
  journal = {Research and Practice in Thrombosis and Haemostasis},
  year = {2026},
  month = aug,
  doi = {10.1016/j.rpth.2026.106902},
  url = {https://doi.org/10.1016/j.rpth.2026.106902},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Von Willebrand factor A2 domain inhibits A1-DNA binding while preserving A1-platelet interaction under flow: evidence from recombinant domain constructs
AU  - Zhitong Peng
AU  - Xiaoxi Sun
AU  - Guangzhou Qu
AU  - Jinhua Fang
AU  - Aiying Liu
AU  - Yuming Huang
AU  - Zhiwei Wu
AU  - Junxian Yang
AU  - Jie Ma
AU  - Jiangguo Lin
PY  - 2026
DA  - 2026/08/01
JO  - Research and Practice in Thrombosis and Haemostasis
DO  - 10.1016/j.rpth.2026.106902
UR  - https://doi.org/10.1016/j.rpth.2026.106902
AB  - Background: Circulating cell-free DNA levels increase in the circulation during inflammation and thrombosis. During immunothrombosis, neutrophil extracellular traps provide long DNA fibers with prothrombotic properties. Von Willebrand factor (VWF) has been reported to interact with DNA via its A1 domain; however, the consequences of this interaction and its regulation by the adjacent A2 domain remain poorly understood. Objectives: Using recombinant VWF domain constructs, we aimed to characterize VWF-A1–DNA interactions and to determine whether the VWF-A2 domain modulates A1–DNA binding and its impact on platelet adhesion under flow. Methods: VWF-A1–DNA interactions were examined using atomic force microscopy, magnetic tweezers, ELISAs, and microfluidic flow assays. Both recombinant A1 and mammalian-expressed A1A2 constructs were employed to assess physiological relevance. Results: VWF-A1 bound to DNA and induced concentration–dependent DNA compaction. DNA binding to VWF-A1 significantly impaired platelet adhesion under flow conditions. In contrast, the A2 domain inhibited VWF-A1–DNA binding, as shown using both isolated A2 and A1A2 constructs, and mitigated DNA’s inhibitory effect on A1-mediated platelet adhesion. Conclusion: These findings suggest that, within recombinant VWF domain constructs, VWF-A1 compacts DNA and that the A2 domain negatively regulates A1–DNA interactions while preserving A1-mediated platelet binding under flow. Although further validation in native multimeric VWF and physiologically relevant models is required, these results provide new insights into how the A2 domain differentially regulates VWF-A1 interactions with DNA and platelets.
SN  - 2475-0379
ER  -