{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:08:54Z","timestamp":1787692134804,"version":"build-2784847793"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["12372312"],"award-info":[{"award-number":["12372312"]}]},{"name":"National Natural Science Foundation of China","award":["12272063"],"award-info":[{"award-number":["12272063"]}]},{"name":"Projects of the \u201cJiangsu Specially-Appointed Professor\u201d","award":["12372312"],"award-info":[{"award-number":["12372312"]}]},{"name":"Projects of the \u201cJiangsu Specially-Appointed Professor\u201d","award":["12272063"],"award-info":[{"award-number":["12272063"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>von Willebrand factor (vWF) is a large glycoprotein in the circulation system, which senses hydrodynamic force at vascular injuries and then recruits platelets in assembling clots. How vWF mechanosenses shear flow for molecular unfolding is an important topic. Here, a F\u00f6rster resonance energy transfer (FRET) biosensor was developed to monitor vWF conformation change to hydrodynamic force. The vWF-based biosensor is anchored on the cell surface, in which the A2 domain is flanked with a FRET pair. With 293T cells seeded into microfluidic channels, 2.8 dyn\/cm2 of shear force (i.e., 28 \u03bcN\/cm2, or 264.1\/s in shear rate) induced a remarkable FRET change (~60%) in 30 min. A gradient micro-shear below 2.8 dyn\/cm2 demonstrated FRET responses positively related to flow magnitudes, with 0.14 dyn\/cm2 (1.4 \u03bcN\/cm2) inducing an obvious change (~16%). The FRET increases indicate closer positioning of A2\u2019s two terminals in vWF or the addition of a more parallel orientation of the FRET pair, supported with the high FRET of the A2-only-based biosensor, which probably resulted from flow-induced A2 dissociation from vWF intramolecular binding such as that in A1\/A3 domains. Interestingly, gradient flow increases from 2.8 to 28 dyn\/cm2 led to decreasing FRET changes, suggesting the second-level unfolding in the A2 domain. The LOCK-vWF biosensor with bridged A2 two terminals or an A2-only biosensor could not sense the shear, indicating a structure-flexible A2 and large vWF molecules that are important in the mechanosensation. In conclusion, the developed vWF-based biosensor demonstrated the high mechanosensation of vWF with two-level unfolding to shear force: the dissociation of the A2 domain from vWF intramolecular binding under a micro-shear, and then the unfolding of A2 in vWF under a higher shear; the FRET response to shear force at a very low scale may support the observed clot formation at microvascular wounds. This study provides new insights into the vWF\u2019s mechanosensitive feature for its physiological functions and implicated disorders.<\/jats:p>","DOI":"10.3390\/bios15040248","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:06:51Z","timestamp":1744621611000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FRET Visualization of High Mechanosensation of von Willebrand Factor to Hydrodynamic Force"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2910-0713","authenticated-orcid":false,"given":"Mingxing","family":"Ouyang","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, 1 Gehu Rd, Wujin District, Changzhou 213164, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, 1 Gehu Rd, Wujin District, Changzhou 213164, China"},{"name":"School of Pharmacy, Changzhou University, Changzhou 213164, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binqian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, 1 Gehu Rd, Wujin District, Changzhou 213164, China"},{"name":"School of Pharmacy, Changzhou University, Changzhou 213164, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, 1 Gehu Rd, Wujin District, Changzhou 213164, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, and Institute of Engineering in Medicine, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shu Chien-Gene Lay Department of Bioengineering, and Institute of Engineering in Medicine, University of California at San Diego, La Jolla, CA 92093, USA"},{"name":"Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1970-8239","authenticated-orcid":false,"given":"Linhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, 1 Gehu Rd, Wujin District, Changzhou 213164, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Neff, A.T., and Sidonio, R.F. (2014). Management of VWD. Hematology 2014, the American Society of Hematology Education Program Book, American Society of Hematology.","DOI":"10.1182\/asheducation-2014.1.536"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Federici, A.B. (2014). Clinical and laboratory diagnosis of VWD. Hematology 2014, the American Society of Hematology Education Program Book, American Society of Hematology.","DOI":"10.1182\/asheducation-2014.1.524"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.thromres.2006.01.014","article-title":"Prophylaxis and von Willebrand\u2019s disease (vWD)","volume":"118","author":"Abshire","year":"2006","journal-title":"Thromb. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Flood, V.H. (2014). New insights into genotype and phenotype of VWD. Hematology 2014, the American Society of Hematology Education Program Book, American Society of Hematology.","DOI":"10.1182\/asheducation-2014.1.531"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/jth.15129","article-title":"Laboratory variability in the diagnosis of type 2 VWD variants","volume":"19","author":"DiGiandomenico","year":"2021","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1055\/s-0042-1754331","article-title":"Laboratory Diagnosis of von Willebrand Disease (VWD): Geographical Perspectives","volume":"48","author":"Favaloro","year":"2022","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/hae.14970","article-title":"Diagnosis and treatment of von Willebrand disease in 2024 and beyond","volume":"30","author":"James","year":"2024","journal-title":"Haemophilia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1182\/blood-2014-06-528406","article-title":"von Willebrand factor biosynthesis, secretion, and clearance: Connecting the far ends","volume":"125","author":"Lenting","year":"2015","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1182\/blood.2022016467","article-title":"Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange","volume":"140","author":"Anderson","year":"2022","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/1076029606291401","article-title":"Characterization of recessive severe type 1 and 3 von Willebrand Disease (VWD), asymptomatic heterozygous carriers versus bloodgroup O-related von Willebrand factor deficiency, and dominant type 1 VWD","volume":"12","author":"Michiels","year":"2006","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1055\/s-0035-1569070","article-title":"Treatment of von Willebrand Disease","volume":"42","author":"Curnow","year":"2016","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1146\/annurev.med.48.1.525","article-title":"Von Willebrand\u2019s disease","volume":"48","author":"Ewenstein","year":"1997","journal-title":"Annu. Rev. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e3038","DOI":"10.1097\/MD.0000000000003038","article-title":"A Laboratory Phenotype\/Genotype Correlation of 1167 French Patients from 670 Families with von Willebrand Disease: A New Epidemiologic Picture","volume":"95","author":"Veyradier","year":"2016","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.thromres.2017.09.025","article-title":"Von Willebrand disease mutation spectrum and associated mutation mechanisms","volume":"159","author":"Eikenboom","year":"2017","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1055\/s-0041-1727282","article-title":"Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis","volume":"47","author":"Favaloro","year":"2021","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/MOH.0000000000000230","article-title":"Regulation of VWF expression, and secretion in health and disease","volume":"23","author":"Xiang","year":"2016","journal-title":"Curr. Opin. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1055\/s-0043-1763259","article-title":"The Role of the von Willebrand Factor Collagen-Binding Assay (VWF:CB) in the Diagnosis and Treatment of von Willebrand Disease (VWD) and Way Beyond: A Comprehensive 36-Year History","volume":"50","author":"Favaloro","year":"2024","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/jth.14729","article-title":"Cleavage by MMP-13 renders VWF unable to bind to collagen but increases its platelet reactivity","volume":"18","author":"Howes","year":"2020","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/978-1-4939-7196-1_31","article-title":"Laboratory Testing for von Willebrand Factor Collagen Binding (VWF:CB)","volume":"1646","author":"Favaloro","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/978-1-0716-3175-1_44","article-title":"Laboratory Testing for von Willebrand Factor Activity by a Glycoprotein Ib-Binding Assay (VWF: GPIbR): HemosIL von Willebrand Factor Ristocetin Cofactor Activity on ACL TOP\u00ae","volume":"2663","author":"Seidizadeh","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1182\/blood-2012-09-455089","article-title":"VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease","volume":"121","author":"Eikenboom","year":"2013","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1111\/j.1538-7836.2012.04797.x","article-title":"Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis","volume":"10","author":"Kanaji","year":"2012","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/ijlh.13785","article-title":"Prognostic value of the ADAMTS13-vWF axis in disseminated intravascular coagulation: Platelet count\/vWF: Ag ratio as a strong prognostic marker","volume":"44","author":"Jang","year":"2022","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_24","first-page":"5636","article-title":"The application of vWF\/ADAMTS13 in essential hypertension","volume":"7","author":"Ma","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1182\/blood.2023019749","article-title":"Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association","volume":"142","author":"Chung","year":"2023","journal-title":"Blood"},{"key":"ref_26","first-page":"319","article-title":"Role of fluid shear stress in regulating VWF structure, function and related blood disorders","volume":"52","author":"Gogia","year":"2015","journal-title":"Biorheology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.thromres.2014.08.013","article-title":"Platelet-free shear flow assay facilitates analysis of shear-dependent functions of VWF and ADAMTS13","volume":"134","author":"Kraus","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bpj.2010.11.084","article-title":"GPIb\u03b1-vWF rolling under shear stress shows differences between type 2B and 2M von Willebrand disease","volume":"100","author":"Coburn","year":"2011","journal-title":"Biophys. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/S0049-3848(08)70028-8","article-title":"VWF attributes\u2013impact on thrombus formation","volume":"122","author":"Reininger","year":"2008","journal-title":"Thromb. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpc.2010.07.002","article-title":"The effect of shear stress on protein conformation: Physical forces operating on biochemical systems: The case of von Willebrand factor","volume":"153","year":"2010","journal-title":"Biophys. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/s41423-023-01042-9","article-title":"Biomechanical control of lymphatic vessel physiology and functions","volume":"20","author":"Angeli","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fcell.2019.00251","article-title":"Biophysics of Cell-Substrate Interactions Under Shear","volume":"7","author":"Paddillaya","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12013-011-9158-8","article-title":"Fluid dynamics of heart development","volume":"61","author":"Santhanakrishnan","year":"2011","journal-title":"Cell Biochem. Biophys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.jmb.2019.02.014","article-title":"Electrostatic Steering Enables Flow-Activated Von Willebrand Factor to Bind Platelet Glycoprotein, Revealed by Single-Molecule Stretching and Imaging","volume":"431","author":"Jiang","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1073\/pnas.1516214113","article-title":"Force sensing by the vascular protein von Willebrand factor is tuned by a strong intermonomer interaction","volume":"113","author":"Mielke","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1039\/D4NR02715A","article-title":"Aptamer-based biotherapeutic conjugate for shear responsive release of Von Willebrand factor A1 domain","volume":"17","author":"Ismail","year":"2025","journal-title":"Nanoscale"},{"key":"ref_37","first-page":"72","article-title":"Platelet glycoprotein Ib\u03b1 forms catch bonds with WT VWF but not with type 2B von Willebrand disease VWF","volume":"45","author":"Wu","year":"2008","journal-title":"Biorheology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jsb.2016.04.012","article-title":"Mutual A domain interactions in the force sensing protein von Willebrand factor","volume":"197","author":"Posch","year":"2017","journal-title":"J. Struct. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1038\/s41467-021-22634-x","article-title":"Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module","volume":"12","author":"Arce","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1182\/blood.2021014729","article-title":"Structural basis of von Willebrand factor multimerization and tubular storage","volume":"139","author":"Zeng","year":"2022","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9226","DOI":"10.1073\/pnas.0903679106","article-title":"Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor","volume":"106","author":"Zhang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1016\/j.bpj.2019.04.025","article-title":"Shear-Induced Extensional Response Behaviors of Tethered von Willebrand Factor","volume":"116","author":"Wang","year":"2019","journal-title":"Biophys. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14353","DOI":"10.1073\/pnas.0807537105","article-title":"Determination of hierarchical relationship of Src and Rac at subcellular locations with FRET biosensors","volume":"105","author":"Ouyang","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ouyang, M.X., Zhou, B.Q., Li, C.M., and Deng, L.H. (2024). Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors. Biosensors, 14.","DOI":"10.20944\/preprints202401.2079.v1"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yoon, S., Pan, Y.J., Shung, K., and Wang, Y.X. (2020). FRET-Based Ca2+ Biosensor Single Cell Imaging Interrogated by High-Frequency Ultrasound. Sensors, 20.","DOI":"10.3390\/s20174998"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"796991","DOI":"10.3389\/fbioe.2021.796991","article-title":"HEK293 Cell Line as a Platform to Produce Recombinant Proteins and Viral Vectors","volume":"9","author":"Tan","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1182\/bloodadvances.2018030122","article-title":"von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain","volume":"3","author":"Zhang","year":"2019","journal-title":"Blood Adv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fphy.2019.00154","article-title":"Fluocell for Ratiometric and High-Throughput Live-Cell Image Visualization and Quantitation","volume":"7","author":"Qin","year":"2019","journal-title":"Front. Phys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/MBC.0000000000000065","article-title":"Update on von Willebrand factor multimers: Focus on high-molecular-weight multimers and their role in hemostasis","volume":"25","author":"Stockschlaeder","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1182\/bloodadvances.2021006405","article-title":"Interaction of von Willebrand factor with blood cells in flow models: A systematic review","volume":"6","author":"Arisz","year":"2022","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17740","DOI":"10.1074\/jbc.M709872200","article-title":"Visualization of polarized membrane type 1 matrix metalloproteinase activity in live cells by fluorescence resonance energy transfer imaging","volume":"283","author":"Ouyang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s44258-024-00034-2","article-title":"FRET verification of crucial interaction sites in RhoA regulation mediated by RhoGDI","volume":"2","author":"Li","year":"2024","journal-title":"Med-X"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1182\/blood.2022016969","article-title":"Conformation of von Willebrand factor in shear flow revealed with stroboscopic single-molecule imaging","volume":"140","author":"Bergal","year":"2022","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"He, Z.C., Li, F., Zuo, P., and Tian, H. (2023). Principles and Applications of Resonance Energy Transfer Involving Noble Metallic Nanoparticles. Materials, 16.","DOI":"10.3390\/ma16083083"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1056\/NEJMoa2002699","article-title":"BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A","volume":"383","author":"Konkle","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1182\/blood.2019001292","article-title":"BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice","volume":"135","author":"Chhabra","year":"2020","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/j.1538-7836.2007.02536.x","article-title":"Purified A2 Domain of von Willebrand Factor Binds to the Active Conformation of von Willebrand Factor and Blocks the Interaction with Platelet Glycoprotein Ib\u03b1","volume":"5","author":"Martin","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.bpj.2009.12.4324","article-title":"Unfolding the A2 Domain of Von Willebrand Factor with the Optical Trap","volume":"98","author":"Ying","year":"2010","journal-title":"Biophys. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1126\/science.1170905","article-title":"Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von Willebrand Factor","volume":"324","author":"Zhang","year":"2009","journal-title":"Sciencce"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e0188405","DOI":"10.1371\/journal.pone.0188405","article-title":"A common mechanism by which type 2A von Willebrand disease mutations enhance ADAMTS13 proteolysis revealed with a von Willebrand factor A2 domain FRET construct","volume":"12","author":"Lynch","year":"2017","journal-title":"PLoS ONE"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/15\/4\/248\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:14:21Z","timestamp":1760030061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/15\/4\/248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["bios15040248"],"URL":"https:\/\/doi.org\/10.3390\/bios15040248","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}