{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:29:10Z","timestamp":1792740550180,"version":"4.5.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,12,18]]},"abstract":"<jats:p>\n                    The pathophysiology of sickle cell disease is complicated by the multiscale processes that link the molecular genotype to the organismal phenotype: hemoglobin polymerization occurring in milliseconds, microscopic cellular sickling in a few seconds or less [Eaton WA, Hofrichter J (1990)\n                    <jats:italic>Adv Protein Chem<\/jats:italic>\n                    40:63\u2013279], and macroscopic vessel occlusion over a time scale of minutes, the last of which is necessary for a crisis [Bunn HF (1997)\n                    <jats:italic>N Engl J Med<\/jats:italic>\n                    337:762\u2013769]. Using a minimal but robust artificial microfluidic environment, we show that it is possible to evoke, control, and inhibit the collective vasoocclusive or jamming event in sickle cell disease. We use a combination of geometric, physical, chemical, and biological means to quantify the phase space for the onset of a jamming event, as well as its dissolution, and find that oxygen-dependent sickle hemoglobin polymerization and melting alone are sufficient to recreate jamming and rescue. We further show that a key source of the heterogeneity in occlusion arises from the slow collective jamming of a confined, flowing suspension of soft cells that change their morphology and rheology relatively quickly. Finally, we quantify and investigate the effects of small-molecule inhibitors of polymerization and therapeutic red blood cell exchange on this dynamical process. Our experimental study integrates the dynamics of collective processes associated with occlusion at the molecular, polymer, cellular, and tissue level; lays the foundation for a quantitative understanding of the rate-limiting processes; and provides a potential tool for optimizing and individualizing treatment, and identifying new therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0707122105","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T20:54:44Z","timestamp":1197492884000},"page":"20496-20500","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":171,"title":["Sickle cell vasoocclusion and rescue in a microfluidic device"],"prefix":"10.1073","volume":"104","author":[{"given":"J. M.","family":"Higgins","sequence":"first","affiliation":[{"name":"*School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138;"},{"name":"Departments of Pathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. T.","family":"Eddington","sequence":"additional","affiliation":[{"name":"Division of Health Sciences and Technology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. N.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115;"},{"name":"Division of Health Sciences and Technology and"},{"name":"Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"*School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA 02138;"},{"name":"**Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,12,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.110.2865.543"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60287-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3603036"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3790.825"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2006.00823.x"},{"key":"e_1_3_3_6_2","volume-title":"Sickle Cell Disease","author":"Serjeant G","year":"2001","unstructured":"G Serjeant, B Serjeant Sickle Cell Disease (Oxford Univ Press, Oxford, 2001)."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371107"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490279410"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490278312"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1534600100"},{"key":"e_1_3_3_11_2","first-page":"53","volume":"8","author":"Chien S","year":"1982","unstructured":"S Chien, RG King, AA Kaperonis, S Usami Blood Cells 8, 53\u201364 (1982).","journal-title":"Blood Cells"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781482268171"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009053534"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-44553"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.2.844"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(80)85121-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.6.1602.1602"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06318.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200353428"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05058"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200305627"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198812013192204"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199507273330402"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4973"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200212000-00002"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac980656z"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2005.04.037"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac060288w"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0707122105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T16:04:35Z","timestamp":1649779475000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0707122105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,18]]},"references-count":28,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2007,12,18]]}},"alternative-id":["10.1073\/pnas.0707122105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0707122105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1097465.553533","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,18]]},"assertion":[{"value":"2007-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}