{"entity": "researcher", "timestamp": "2026-08-22T06:56:01.681Z", "family": "Duval", "given": "C\u00e9dric", "initials": "C", "orcid": "0000-0002-4870-6542", "affiliations": ["Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/77dcb145cb6f4f1cb82a25dd5083c685.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/77dcb145cb6f4f1cb82a25dd5083c685"}}, "publications": [{"entity": "publication", "iuid": "4eea4040063f47508f997ef5ffbbfe70", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4eea4040063f47508f997ef5ffbbfe70.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4eea4040063f47508f997ef5ffbbfe70"}}, "title": "Fibrin protofibril packing and clot stability are enhanced by extended knob-hole interactions and catch-slip bonds.", "authors": [{"family": "Asquith", "given": "Nathan L", "initials": "NL", "orcid": "0000-0002-7073-825X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84be15656520480da5cfda90b0e19960.json"}}, {"family": "Duval", "given": "C\u00e9dric", "initials": "C", "orcid": "0000-0002-4870-6542", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77dcb145cb6f4f1cb82a25dd5083c685.json"}}, {"family": "Zhmurov", "given": "Artem", "initials": "A"}, {"family": "Baker", "given": "Stephen R", "initials": "SR"}, {"family": "McPherson", "given": "Helen R", "initials": "HR"}, {"family": "Domingues", "given": "Marco M", "initials": "MM", "orcid": "0000-0003-1502-1421", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dba826627a0f4aa3b3fcf066062f068f.json"}}, {"family": "Connell", "given": "Simon D A", "initials": "SDA", "orcid": "0000-0003-2500-5724", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8ae885005aa4e9180dbb1eb6cd1768f.json"}}, {"family": "Barsegov", "given": "Valeri", "initials": "V", "orcid": "0000-0003-1994-3917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/33b7a06470d94cd894d848ebd2eea2f2.json"}}, {"family": "Ari\u00ebns", "given": "Robert A S", "initials": "RAS", "orcid": "0000-0002-6310-5745", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2230c5071da44bb9a10a7693dfcdf36b.json"}}], "type": "journal article", "published": "2022-07-12", "journal": {"title": "Blood Adv", "issn": "2473-9529", "volume": "6", "issue": "13", "pages": "4015-4027", "issn-l": null}, "abstract": "Fibrin polymerization involves thrombin-mediated exposure of knobs on one monomer that bind to holes available on another, leading to the formation of fibers. In silico evidence has suggested that the classical A:a knob-hole interaction is enhanced by surrounding residues not directly involved in the binding pocket of hole a, via noncovalent interactions with knob A. We assessed the importance of extended knob-hole interactions by performing biochemical, biophysical, and in silico modeling studies on recombinant human fibrinogen variants with mutations at residues responsible for the extended interactions. Three single fibrinogen variants, \u03b3D297N, \u03b3E323Q, and \u03b3K356Q, and a triple variant \u03b3DEK (\u03b3D297N/\u03b3E323Q/\u03b3K356Q) were produced in a CHO (Chinese Hamster Ovary) cell expression system. Longitudinal protofibril growth probed by atomic force microscopy was disrupted for \u03b3D297N and enhanced for the \u03b3K356Q mutation. Initial polymerization rates were reduced for all variants in turbidimetric studies. Laser scanning confocal microscopy showed that \u03b3DEK and \u03b3E323Q produced denser clots, whereas \u03b3D297N and \u03b3K356Q were similar to wild type. Scanning electron microscopy and light scattering studies showed that fiber thickness and protofibril packing of the fibers were reduced for all variants. Clot viscoelastic analysis showed that only \u03b3DEK was more readily deformable. In silico modeling suggested that most variants displayed only slip-bond dissociation kinetics compared with biphasic catch-slip kinetics characteristics of wild type. These data provide new evidence for the role of extended interactions in supporting the classical knob-hole bonds involving catch-slip behavior in fibrin formation, clot structure, and clot mechanics.", "doi": "10.1182/bloodadvances.2022006977", "pmid": "35561308", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9278297"}, {"db": "pii", "key": "485243"}], "notes": [], "created": "2026-08-21T12:33:17.759Z", "modified": "2026-08-21T12:33:18.432Z"}]}