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dc.contributor.authorPapageorgiou, Dimitrios P.en
dc.contributor.authorAbidi, Sabia Z.en
dc.contributor.authorChang, Hung-Yuen
dc.contributor.authorLi, Xuejinen
dc.contributor.authorKato, Gregory J.en
dc.contributor.authorKarniadakis, George E.en
dc.contributor.authorSuresh, Subraen
dc.contributor.authorDao, Mingen
dc.identifier.citationPapageorgiou, D. P., Abidi, S. Z., Chang, H.-Y., Li, X., Kato, G. J., Karniadakis, G. E., . . . Dao, M. (2018). Simultaneous polymerization and adhesion under hypoxia in sickle cell disease. Proceedings of the National Academy of Sciences, 115(38), 9473-9478. doi:10.1073/pnas.1807405115en
dc.description.abstractPolymerization and adhesion, dynamic processes that are hallmarks of sickle cell disease (SCD), have thus far been studied in vitro only separately. Here, we present quantitative results of the simultaneous and synergistic effects of adhesion and polymerization of deoxygenated sickle hemoglobin (HbS) in the human red blood cell (RBC) on the mechanisms underlying vasoocclusive pain crisis. For this purpose, we employ a specially developed hypoxic microfluidic platform, which is capable of inducing sickling and unsickling of RBCs in vitro, to test blood samples from eight patients with SCD. We supplemented these experimental results with detailed molecular-level computational simulations of cytoadherence and biorheology using dissipative particle dynamics. By recourse to image analysis techniques, we characterize sickle RBC maturation stages in the following order of the degree of adhesion susceptibility under hypoxia: sickle reticulocytes in circulation (SRs) → sickle mature erythrocytes (SMEs) → irreversibly sickled cells (ISCs). We show that (i) hypoxia significantly enhances sickle RBC adherence; (ii) HbS polymerization enhances sickle cell adherence in SRs and SMEs, but not in ISCs; (iii) SRs exhibit unique adhesion dynamics where HbS fiber projections growing outward from the cell surface create multiple sites of adhesion; and (iv) polymerization stimulates adhesion and vice versa, thereby establishing the bidirectional coupling between the two processes. These findings offer insights into possible mechanistic pathways leading to vasoocclusion crisis. They also elucidate the processes underlying the onset of occlusion that may involve circulating reticulocytes, which are more abundant in hemolytic anemias due to robust compensatory erythropoiesis.en
dc.format.extent6 p.en
dc.relation.ispartofseriesProceedings of the National Academy of Sciencesen
dc.rights© 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en
dc.subjectDissipative Particle Dynamicsen
dc.subjectSickle Cell Adhesion Dynamicsen
dc.titleSimultaneous polymerization and adhesion under hypoxia in sickle cell diseaseen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Materials Science & Engineeringen
dc.description.versionPublished versionen
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