دورية أكاديمية
Simultaneous polymerization and adhesion under hypoxia in sickle cell disease.
| العنوان: | Simultaneous polymerization and adhesion under hypoxia in sickle cell disease. |
|---|---|
| المؤلفون: | Papageorgiou DP; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139., Abidi SZ; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139., Chang HY; Division of Applied Mathematics, Brown University, Providence, RI 02912., Li X; Division of Applied Mathematics, Brown University, Providence, RI 02912., Kato GJ; Department of Medicine, Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261., Karniadakis GE; Division of Applied Mathematics, Brown University, Providence, RI 02912., Suresh S; Nanyang Technological University, Singapore 639798 ssuresh@ntu.edu.sg mingdao@mit.edu., Dao M; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; ssuresh@ntu.edu.sg mingdao@mit.edu. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Sep 18; Vol. 115 (38), pp. 9473-9478. Date of Electronic Publication: 2018 Sep 06. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Anemia, Sickle Cell/*blood , Erythrocytes/*metabolism , Erythrocytes, Abnormal/*metabolism , Hemoglobin, Sickle/*metabolism, Anemia, Sickle Cell/pathology ; Cell Adhesion ; Cell Hypoxia ; Humans ; Hypoxia ; Microfluidics/methods ; Polymerization ; Reticulocytes/metabolism |
| مستخلص: | Polymerization 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. Competing Interests: Conflict of interest statement: D.P.P., S.Z.A., M.D., and S.S. have filed a patent based on the work presented in this paper. (Copyright © 2018 the Author(s). Published by PNAS.) |
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| معلومات مُعتمدة: | P41 EB015871 United States EB NIBIB NIH HHS; R01 HL121386 United States HL NHLBI NIH HHS; U01 HL114476 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: HbS polymerization; dissipative particle dynamics; hypoxia; microfluidics; sickle cell adhesion dynamics |
| المشرفين على المادة: | 0 (Hemoglobin, Sickle) |
| تواريخ الأحداث: | Date Created: 20180908 Date Completed: 20181011 Latest Revision: 20190312 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6156668 |
| DOI: | 10.1073/pnas.1807405115 |
| PMID: | 30190429 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
|---|---|
| DOI: | 10.1073/pnas.1807405115 |