{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:35:30Z","timestamp":1772811330812,"version":"3.50.1"},"reference-count":32,"publisher":"Proceedings of the National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,27]]},"abstract":"<jats:p>\n            Carbohydrate\u2013protein bonds interrupt the rapid flow of leukocytes\n in the circulation by initiation of rolling and tethering at vessel\n walls. The cell surface carbohydrate ligands are glycosylated proteins\n like the mucin P-selectin glycoprotein ligand-1 (PSGL-1), which bind\n ubiquitously to the family of E-, P-, and L-selectin proteins in\n membranes of leukocytes and endothelium. The current view is that\n carbohydrate\u2013selectin bonds dissociate a few times per second, and the\n unbinding rate increases weakly with force. However, such studies have\n provided little insight into how numerous hydrogen bonds, a\n Ca\n            <jats:sup>2+<\/jats:sup>\n            metal ion bond, and other interactions contribute to\n the mechanical strength of these attachments. Decorating a force probe\n with very dilute ligands and controlling touch to achieve rare\n single-bond events, we have varied the unbinding rates of\n carbohydrate\u2013selectin bonds by detachment with ramps of force\/time\n from 10 to 100,000 pN\/sec. Testing PSGL-1, its outer 19 aa (19FT),\n and sialyl Lewis\n            <jats:sup>X<\/jats:sup>\n            (sLe\n            <jats:sup>X<\/jats:sup>\n            ) against L-selectin\n            <jats:italic>in vitro<\/jats:italic>\n            on glass microspheres and\n            <jats:italic>in\n situ<\/jats:italic>\n            on neutrophils, we found that the unbinding rates followed\n the same dependence on force and increased by nearly 1,000-fold as\n rupture forces rose from a few to \u2248200 pN. Plotted on a logarithmic\n scale of loading rate, the rupture forces reveal two prominent energy\n barriers along the unbinding pathway. Strengths above 75 pN arise from\n rapid detachment (&lt;0.01 sec) impeded by an inner barrier that requires\n a Ca\n            <jats:sup>2+<\/jats:sup>\n            bond between a single sLe\n            <jats:sup>X<\/jats:sup>\n            and the\n lectin domain. Strengths below 75 pN occur under slow detachment\n (&gt;0.01 sec) impeded by the outer barrier, which appears to involve an\n array of weak (putatively hydrogen) bonds.\n          <\/jats:p>","DOI":"10.1073\/pnas.061324998","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:36:44Z","timestamp":1027694204000},"page":"3784-3789","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":186,"title":["Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force"],"prefix":"10.1073","volume":"98","author":[{"given":"Evan","family":"Evans","sequence":"first","affiliation":[{"name":"Departments of Physics and Pathology, University of\r British Columbia, Vancouver, BC, Canada V6T 2A6;\r Department of Biomedical Engineering, Boston University,\r Boston, MA 02215; Department of Biomedical Engineering,\r University of Pennsylvania, Philadelphia, PA 19104; and\r Department of Biomedical Engineering, University of\r California, Davis, CA 95616"}]},{"given":"Andrew","family":"Leung","sequence":"additional","affiliation":[{"name":"Departments of Physics and Pathology, University of\r British Columbia, Vancouver, BC, Canada V6T 2A6;\r Department of Biomedical Engineering, Boston University,\r Boston, MA 02215; Department of Biomedical Engineering,\r University of Pennsylvania, Philadelphia, PA 19104; and\r Department of Biomedical Engineering, University of\r California, Davis, CA 95616"}]},{"given":"Dan","family":"Hammer","sequence":"additional","affiliation":[{"name":"Departments of Physics and Pathology, University of\r British Columbia, Vancouver, BC, Canada V6T 2A6;\r Department of Biomedical Engineering, Boston University,\r Boston, MA 02215; Department of Biomedical Engineering,\r University of Pennsylvania, Philadelphia, PA 19104; and\r Department of Biomedical Engineering, University of\r California, Davis, CA 95616"}]},{"given":"Scott","family":"Simon","sequence":"additional","affiliation":[{"name":"Departments of Physics and Pathology, University of\r British Columbia, Vancouver, BC, Canada V6T 2A6;\r Department of Biomedical Engineering, Boston University,\r Boston, MA 02215; Department of Biomedical Engineering,\r University of Pennsylvania, Philadelphia, PA 19104; and\r Department of Biomedical Engineering, University of\r California, Davis, CA 95616"}]}],"member":"341","published-online":{"date-parts":[[2001,3,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90393-D"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.17.7538"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/346425a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90337-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.12.1965"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90327-M"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.117.4.895"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90173-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13771"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00138-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81563-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/374539a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.5.1169"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11631"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79487-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77169-9"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.347575"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.21.12283"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78802-7"},{"key":"e_1_3_3_20_2","first-page":"1","volume":"111","author":"Evans 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