{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:33:32Z","timestamp":1777250012134,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012705","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL154150"],"award-info":[{"award-number":["R01HL154150"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Laboratory of Excellence GR-Ex","award":["ANR-11-LABX-0051"],"award-info":[{"award-number":["ANR-11-LABX-0051"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Gaucher Disease (GD) is a rare genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucosylceramide in various cells, including red blood cells (RBCs). This accumulation results in altered biomechanical properties and rheological behavior of RBCs, which may play an important role in blood rheology and the development of bone infarcts, avascular necrosis (AVN) and other bone diseases associated with GD. In this study, dissipative particle dynamics (DPD) simulations are employed to investigate the biomechanics and rheology of blood and RBCs in GD under various flow conditions. The model incorporates the unique characteristics of GD RBCs, such as decreased deformability and increased aggregation properties, and aims to capture the resulting changes in RBC biophysics and blood viscosity. This study is the first to explore the Young\u2019s modulus and aggregation parameters of GD RBCs by validating simulations with confocal imaging and experimental RBC disaggregation thresholds. Through\n                    <jats:italic>in silico<\/jats:italic>\n                    simulations, we examine the impact of hematocrit, RBC disaggregation threshold, and cell stiffness on blood viscosity in GD. The results reveal three distinct domains of GD blood viscosity based on shear rate: the aggregation domain, where the RBC disaggregation threshold predominantly influences blood viscosity; the transition area, where both RBC aggregation and stiffness impact on blood viscosity; and the stiffness domain, where the stiffness of RBCs emerges as the primary determinant of blood viscosity. By analyzing RBC mechanical properties and blood viscosity in relation to bone disease, we find that the RBC aggregation properties, deformability, and blood viscosity, may contribute to its onset. These findings enhance our understanding of how changes in RBC properties impact on blood viscosity and may affect bone health, offering a partial explanation for the bone complications observed in GD patients.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1012705","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T17:55:24Z","timestamp":1757526924000},"page":"e1012705","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["In silico biophysics and rheology of blood and red blood cells in Gaucher Disease"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-247X","authenticated-orcid":true,"given":"Zhaojie","family":"Chai","sequence":"first","affiliation":[]},{"given":"Guansheng","family":"Li","sequence":"additional","affiliation":[]},{"given":"Papa Alioune","family":"Ndour","sequence":"additional","affiliation":[]},{"given":"Philippe","family":"Connes","sequence":"additional","affiliation":[]},{"given":"Pierre A.","family":"Buffet","sequence":"additional","affiliation":[]},{"given":"Melanie","family":"Franco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-7120","authenticated-orcid":true,"given":"George Em","family":"Karniadakis","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"issue":"843","key":"pcbi.1012705.ref001","first-page":"10","article-title":"Defective sphingolipids metabolism and tumor associated macrophages as the possible links between gaucher disease and blood cancer development","volume":"20","author":"M Watek","year":"2019","journal-title":"Int J Mol Sci."},{"issue":"9645","key":"pcbi.1012705.ref002","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(08)61522-6","article-title":"Phenotype, diagnosis, and treatment of Gaucher\u2019s disease","volume":"372","author":"GA Grabowski","year":"2008","journal-title":"The Lancet."},{"key":"pcbi.1012705.ref003","first-page":"72","article-title":"Gaucher disease: the metabolic defect, pathophysiology, phenotypes and natural history","volume":"12","author":"HN Baris","year":"2014","journal-title":"Pediatric endocrinology reviews: PER."},{"issue":"2","key":"pcbi.1012705.ref004","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3390\/ijms18020441","article-title":"A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments","volume":"18","author":"J Stirnemann","year":"2017","journal-title":"International Journal of molecular sciences."},{"issue":"2","key":"pcbi.1012705.ref005","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymgme.2020.12.291","article-title":"Gaucher disease: Basic and translational science needs for more complete therapy and management","volume":"132","author":"GA Grabowski","year":"2021","journal-title":"Molecular Genetics and Metabolism."},{"issue":"3","key":"pcbi.1012705.ref006","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1309\/BG5VA8JRDQH1M7HN","article-title":"Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages","volume":"122","author":"LA Boven","year":"2004","journal-title":"American journal of clinical pathology."},{"issue":"14","key":"pcbi.1012705.ref007","doi-asserted-by":"crossref","first-page":"7640","DOI":"10.3390\/ijms23147640","article-title":"Phagocytosis of erythrocytes from gaucher patients induces phenotypic modifications in macrophages, driving them toward gaucher cells","volume":"23","author":"L Dupuis","year":"2022","journal-title":"International Journal of Molecular Sciences."},{"issue":"3","key":"pcbi.1012705.ref008","first-page":"546","article-title":"Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease","volume":"12","author":"M Franco","year":"2013","journal-title":"Blood, The Journal of the American Society of Hematology."},{"issue":"6","key":"pcbi.1012705.ref009","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/jbmr.3734","article-title":"Gaucher disease in bone: from pathophysiology to practice","volume":"34","author":"D Hughes","year":"2019","journal-title":"Journal of Bone and Mineral Research."},{"issue":"5","key":"pcbi.1012705.ref010","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.jbspin.2006.01.025","article-title":"Pathophysiology and natural history of avascular necrosis of bone","volume":"73","author":"P Lafforgue","year":"2006","journal-title":"Joint Bone Spine."},{"key":"pcbi.1012705.ref011","article-title":"Gaucher disease with pathological femoral neck fracture","volume":"2013","author":"E Binnetoglu","year":"2013","journal-title":"Case Reports."},{"issue":"6","key":"pcbi.1012705.ref012","doi-asserted-by":"crossref","DOI":"10.1002\/ajh.25453","article-title":"Spontaneous healing of avascular necrosis of the femoral head in sickle cell disease","volume":"94","author":"NP Itzep","year":"2019","journal-title":"Am J Hematol."},{"issue":"2","key":"pcbi.1012705.ref013","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1006\/bcmd.2002.0517","article-title":"Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy","volume":"28","author":"R Schiffmann","year":"2002","journal-title":"Blood Cells, Molecules, and Diseases."},{"issue":"2","key":"pcbi.1012705.ref014","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3233\/CH-2008-1121","article-title":"Increased red blood cell aggregation in patients with Gaucher disease is non-inflammatory","volume":"40","author":"T Adar","year":"2008","journal-title":"Clinical hemorheology and microcirculation."},{"issue":"12","key":"pcbi.1012705.ref015","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.3324\/haematol.2016.147546","article-title":"Unexpected macrophage-independent dyserythropoiesis in Gaucher disease","volume":"101","author":"N Reihani","year":"2016","journal-title":"Haematologica."},{"key":"pcbi.1012705.ref016","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.chroma.2017.10.038","article-title":"Optimization of ultra-high pressure liquid chromatography\u2013tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher\u2019s disease","volume":"1525","author":"C Chipeaux","year":"2017","journal-title":"Journal of Chromatography a."},{"issue":"4","key":"pcbi.1012705.ref017","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1365-2141.2006.06199.x","article-title":"Aggregation of red blood cells in patients with Gaucher disease","volume":"134","author":"T Adar","year":"2006","journal-title":"British journal of haematology."},{"issue":"8","key":"pcbi.1012705.ref018","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1002\/jbmr.1680","article-title":"Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry","volume":"27","author":"A Khan","year":"2012","journal-title":"Journal of Bone and Mineral Research."},{"issue":"1","key":"pcbi.1012705.ref019","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/BF02916121","article-title":"Deformability of red blood cells: A determinant of blood viscosity","volume":"19","author":"S Shin","year":"2005","journal-title":"Journal of Mechanical Science and Technology."},{"issue":"3","key":"pcbi.1012705.ref020","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-0609.2005.00496.x","article-title":"Haemorheology in Gaucher disease","volume":"75","author":"BE Bax","year":"2005","journal-title":"European Journal of Haematology."},{"issue":"7","key":"pcbi.1012705.ref021","doi-asserted-by":"crossref","first-page":"11854","DOI":"10.1021\/acsnano.1c02957","article-title":"Glucosylceramide Associated with Gaucher Disease Forms Amyloid-like Twisted Ribbon Fibrils That Induce -Synuclein Aggregation","volume":"15","author":"A Paul","year":"2021","journal-title":"ACS Nano."},{"issue":"10","key":"pcbi.1012705.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0077235","article-title":"Membrane lipid co-aggregation with -synuclein fibrils","volume":"8","author":"E Hellstrand","year":"2013","journal-title":"PloS one."},{"issue":"11","key":"pcbi.1012705.ref023","doi-asserted-by":"crossref","first-page":"114108","DOI":"10.1063\/1.5037991","article-title":"Experimental characterization of an extended electrohydrodynamic cone-jet with a hemispherical nozzle","volume":"30","author":"A Rajabi","year":"2018","journal-title":"Physics of Fluid"},{"issue":"1","key":"pcbi.1012705.ref024","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1039\/C2SM26891D","article-title":"Continuum-and particle-based modeling of shapes and dynamics of red blood cells in health and disease","volume":"9","author":"X Li","year":"2013","journal-title":"Soft matter."},{"issue":"175","key":"pcbi.1012705.ref025","doi-asserted-by":"crossref","first-page":"20200834","DOI":"10.1098\/rsif.2020.0834","article-title":"Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood","volume":"18","author":"A Yazdani","year":"2021","journal-title":"Journal of The Royal Society Interface."},{"issue":"13","key":"pcbi.1012705.ref026","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1016\/j.bpj.2021.05.013","article-title":"In silico biophysics and hemorheology of blood hyperviscosity syndrome","volume":"120","author":"E Javadi","year":"2021","journal-title":"Biophysical Journal."},{"key":"pcbi.1012705.ref027"},{"issue":"2","key":"pcbi.1012705.ref028","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10237-013-0497-9","article-title":"Multiscale modeling of blood flow: From single cells to blood rheology","volume":"13","author":"DA Fedosov","year":"2014","journal-title":"Biomechanics and Modeling in Mechanobiology."},{"key":"pcbi.1012705.ref029","doi-asserted-by":"crossref","first-page":"109031","DOI":"10.1016\/j.jcp.2019.109031","article-title":"Parallel modeling of cell suspension flow in complex micro-networks with inflow\/outflow boundary conditions","volume":"401","author":"G Li","year":"2020","journal-title":"Journal of Computational Physics."},{"key":"pcbi.1012705.ref030","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.bpj.2023.05.022","article-title":"In silico and in vitro study of the adhesion dynamics of erythrophagocytosis in sickle cell disease","volume":"122","author":"G Li","year":"2023","journal-title":"Biophysical Journal."},{"issue":"21","key":"pcbi.1012705.ref031","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1016\/j.bpj.2021.09.038","article-title":"Computational modeling of biomechanics and biorheology of heated red blood cells","volume":"120","author":"ZL Liu","year":"2021","journal-title":"Biophysical Journal."},{"issue":"5","key":"pcbi.1012705.ref032","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1557\/mrs2010.571","article-title":"Shape and biomechanical characteristics of human red blood cells in health and disease","volume":"35","author":"M Diez-Silva","year":"2010","journal-title":"MRS bulletin."},{"issue":"5","key":"pcbi.1012705.ref033","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.bpj.2020.07.026","article-title":"Quantifying Fibrinogen-Dependent Aggregation of Red Blood Cells in Type 2 Diabetes Mellitus","volume":"119","author":"Y Deng","year":"2020","journal-title":"Biophysical Journal."},{"key":"pcbi.1012705.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pcbi.1002270","article-title":"Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria","volume":"7","author":"DA Fedosov","year":"2011","journal-title":"PLOS Computational Biology."},{"issue":"2","key":"pcbi.1012705.ref035","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.bpj.2017.06.015","article-title":"Modeling of Biomechanics and Biorheology of Red Blood Cells in Type 2 Diabetes Mellitus","volume":"113","author":"HY Chang","year":"2017","journal-title":"Biophysical Journal."},{"key":"pcbi.1012705.ref036","doi-asserted-by":"crossref","unstructured":"Baskurt O, Neu B, Meiselman HJ. Red blood cell aggregation. 2011.","DOI":"10.1201\/b11221"},{"issue":"7","key":"pcbi.1012705.ref037","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1115\/1.2112907","article-title":"Computational fluid dynamic simulation of aggregation of deformable cells in a shear flow","volume":"127","author":"P Bagchi","year":"2005","journal-title":"Journal of biomechanical engineering."},{"issue":"12","key":"pcbi.1012705.ref038","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/fld.798","article-title":"Coupling of Navier\u2013Stokes equations with protein molecular dynamics and its application to hemodynamics","volume":"46","author":"Y Liu","year":"2004","journal-title":"International Journal for Numerical Methods in Fluids."},{"issue":"1","key":"pcbi.1012705.ref039","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jcp.2006.05.010","article-title":"Rheology of red blood cell aggregation by computer simulation","volume":"220","author":"Y Liu","year":"2006","journal-title":"Journal of Computational Physics."},{"issue":"1","key":"pcbi.1012705.ref040","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jbiomech.2007.07.020","article-title":"Red blood cell aggregation and dissociation in shear flows simulated by lattice Boltzmann method","volume":"41","author":"J Zhang","year":"2008","journal-title":"Journal of biomechanics."},{"issue":"1","key":"pcbi.1012705.ref041","doi-asserted-by":"crossref","first-page":"7928","DOI":"10.1038\/s41598-017-07634-6","article-title":"The buckling instability of aggregating red blood cells","volume":"7","author":"D Flormann","year":"2017","journal-title":"Scientific reports."},{"issue":"1","key":"pcbi.1012705.ref042","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1038\/srep04348","article-title":"The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows","volume":"4","author":"M Brust","year":"2014","journal-title":"Scientific reports."},{"key":"pcbi.1012705.ref043","first-page":"439","article-title":"Basic phenomena of red blood cell rouleaux formation","volume":"36","author":"H B\u00e4umler","year":"1999","journal-title":"Biorheology."},{"issue":"6","key":"pcbi.1012705.ref044","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1063\/1.1747782","article-title":"The Statistical Mechanical Theory of Transport Processes. IV. The Equations of Hydrodynamics","volume":"18","author":"JH Irving","year":"1950","journal-title":"The Journal of Chemical Physics."},{"issue":"1","key":"pcbi.1012705.ref045","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.actbio.2004.09.001","article-title":"Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria","volume":"1","author":"S Suresh","year":"2005","journal-title":"Acta biomaterialia."},{"key":"pcbi.1012705.ref046"},{"issue":"2","key":"pcbi.1012705.ref047","first-page":"0210081","article-title":"Computational biomechanics of human red blood cells in hematological disorders","volume":"139","author":"X Li","year":"2017","journal-title":"Journal of biomechanical engineering."},{"key":"pcbi.1012705.ref048","doi-asserted-by":"crossref","unstructured":"Skalak R, Keller SR, Secomb TW. ASME centennial historical perspective paper: mechanics of blood flow. 1981.","DOI":"10.1115\/1.3138253"},{"issue":"2","key":"pcbi.1012705.ref049","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/CH-2009-1202","article-title":"New guidelines for hemorheological laboratory techniques","volume":"42","author":"O Baskurt","year":"2009","journal-title":"Clinical Hemorheology and Microcirculation."},{"issue":"3934","key":"pcbi.1012705.ref050","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1126\/science.168.3934.977","article-title":"Shear Dependence of Effective Cell Volume as a Determinant of Blood Viscosity","volume":"168","author":"S Chien","year":"1970","journal-title":"Science."},{"key":"pcbi.1012705.ref051","first-page":"305","article-title":"Mechanics of blood flow in the microcirculation","volume":"49","author":"TW Secomb","year":"1995","journal-title":"Symposia of the Society for Experimental Biology."},{"key":"pcbi.1012705.ref052","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev.fluid.29.1.399","article-title":"Blood flow in arteries","volume":"29","author":"DN Ku","year":"1997","journal-title":"Annual Review of Fluid Mechanics."},{"key":"pcbi.1012705.ref053","doi-asserted-by":"crossref","unstructured":"Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. In: Seminars in thrombosis and hemostasis. vol. 29. Thieme Medical Publishers, Inc.; 2003. p. 435\u2013450.","DOI":"10.1055\/s-2003-44551"},{"issue":"1","key":"pcbi.1012705.ref054","doi-asserted-by":"crossref","first-page":"9384","DOI":"10.1038\/s41598-023-36633-z","article-title":"Blood viscosity associated with stroke mechanism and early neurological deterioration in middle cerebral artery atherosclerosis","volume":"13","author":"HG Woo","year":"2023","journal-title":"Scientific Reports."},{"key":"pcbi.1012705.ref055","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.actatropica.2016.03.001","article-title":"Cytokine modulation of human blood viscosity from vivax malaria patients","volume":"158","author":"EF Scherer","year":"2016","journal-title":"Acta Tropica."},{"issue":"1","key":"pcbi.1012705.ref056","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF00138264","article-title":"Comparative evaluation of blood viscosity in diabetic retinopathy","volume":"7","author":"M Peduzzi","year":"1984","journal-title":"International Ophthalmology."},{"key":"pcbi.1012705.ref057","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.bpj.2018.12.008","article-title":"Quantifying Shear-Induced Deformation and Detachment of Individual Adherent Sickle Red Blood Cells","volume":"116","author":"Y Deng","year":"2019","journal-title":"Biophyscal Journal."},{"key":"pcbi.1012705.ref058","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.3389\/fphys.2019.01329","article-title":"Blood rheology: key parameters, impact on blood flow, role in sickle cell disease and effects of exercise","volume":"10","author":"E Nader","year":"2019","journal-title":"Frontiers in physiology."},{"issue":"5","key":"pcbi.1012705.ref059","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.berh.2011.10.015","article-title":"Gaucher disease and bone","volume":"25","author":"P Mikosch","year":"2011","journal-title":"Best Practice & Research Clinical Rheumatology."},{"key":"pcbi.1012705.ref060","doi-asserted-by":"crossref","DOI":"10.1259\/bjr.75.suppl_1.750002","article-title":"Skeletal aspects of Gaucher disease: a review","volume":"75","author":"RJ Wenstrup","year":"2002","journal-title":"The British Journal of Radiology."},{"key":"pcbi.1012705.ref061","doi-asserted-by":"crossref","first-page":"1320773","DOI":"10.3389\/fneur.2023.1320773","article-title":"High blood viscosity in acute ischemic stroke","volume":"14","author":"J Kang","year":"2023","journal-title":"Frontiers in Neurology."},{"issue":"4","key":"pcbi.1012705.ref062","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/j.1365-2141.1992.tb02998.x","article-title":"Rheological changes in the prodromal and established phases of sickle cell vaso-occlusive crisis","volume":"81","author":"N Akinola","year":"1992","journal-title":"British journal of haematology."},{"key":"pcbi.1012705.ref063"},{"issue":"2","key":"pcbi.1012705.ref064","article-title":"The role of blood viscosity in infectious diseases","volume":"12","author":"GD Sloop","year":"2020","journal-title":"Cureus."},{"issue":"8","key":"pcbi.1012705.ref065","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1182\/blood.V79.8.2154.2154","article-title":"Red blood cell changes during the evolution of the sickle cell painful crisis","volume":"79","author":"SK Ballas","year":"1992","journal-title":"Blood."},{"key":"pcbi.1012705.ref066","article-title":"rare case of avascular necrosis in sickle cell trait: a case report","volume":"18","author":"WJ. A Sanders","year":"2018","journal-title":"BMC Hematology."},{"issue":"4","key":"pcbi.1012705.ref067","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.3390\/ijms23042247","article-title":"Red blood cell morphodynamics in patients with polycythemia Vera and stroke","volume":"23","author":"PI Kuznetsova","year":"2022","journal-title":"International Journal of Molecular Sciences."},{"issue":"12","key":"pcbi.1012705.ref068","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1039\/D0LC00112K","article-title":"Microfluidic assessment of red blood cell mediated microvascular occlusion","volume":"20","author":"Y Man","year":"2020","journal-title":"Lab on a Chip."},{"key":"pcbi.1012705.ref069","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3389\/fphys.2014.00084","article-title":"Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging","volume":"5","author":"JG Mohanty","year":"2014","journal-title":"Frontiers in physiology."},{"issue":"10","key":"pcbi.1012705.ref070","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.bpj.2017.04.020","article-title":"OpenRBC: A fast simulator of red blood cells at protein resolution","volume":"112","author":"YH Tang","year":"2017","journal-title":"Biophysical journal."},{"key":"pcbi.1012705.ref071","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jbiomech.2016.11.019","article-title":"A multiscale biomechanical model of platelets: Correlating with in-vitro results","volume":"50","author":"P Zhang","year":"2017","journal-title":"Journal of biomechanics."},{"issue":"14","key":"pcbi.1012705.ref072","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1039\/D2SM01602H","article-title":"Dynamics of the axon plasma membrane skeleton","volume":"19","author":"Z Chai","year":"2023","journal-title":"Soft Matter."},{"issue":"18","key":"pcbi.1012705.ref073","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1016\/j.bpj.2022.08.027","article-title":"The periodic axon membrane skeleton leads to Na nanodomains but does not impact action potentials","volume":"121","author":"Z Chai","year":"2022","journal-title":"Biophysical Journal."},{"issue":"10","key":"pcbi.1012705.ref074","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005173","article-title":"MD\/DPD multiscale framework for predicting morphology and stresses of red blood cells in health and disease","volume":"12","author":"HY Chang","year":"2016","journal-title":"PLoS computational biology."},{"key":"pcbi.1012705.ref075","doi-asserted-by":"crossref","first-page":"031903","DOI":"10.1063\/1.5144436","article-title":"Numerical design of a highly efficient microfluidic chip for blood plasma separation","volume":"32","author":"G Li","year":"2020","journal-title":"Physics of Fluids."},{"key":"pcbi.1012705.ref076","doi-asserted-by":"crossref","unstructured":"Fedosov DA, Caswell B, Suresh S, Karniadakis GE. Quantifying the biophysical characteristics of <i>Plasmodium-falciparum<\/i>-parasitized red blood cells in microcirculation. Proceedings of the National Academy of Sciences. 2011;108(1):35\u201339.","DOI":"10.1073\/pnas.1009492108"},{"issue":"2","key":"pcbi.1012705.ref077","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bpj.2011.12.006","article-title":"Quantifying the Rheological and Hemodynamic Characteristics of Sickle Cell Anemia","volume":"102","author":"H Lei","year":"2012","journal-title":"Biophysical Journal."},{"issue":"4","key":"pcbi.1012705.ref078","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/ajh.20011","article-title":"Rheological determinants in patients with Gaucher disease and internal inflammation","volume":"75","author":"A Zimran","year":"2004","journal-title":"American Journal of Hematology."},{"issue":"1","key":"pcbi.1012705.ref079","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jpedsurg.2015.10.028","article-title":"Hematologic outcomes after total splenectomy and partial splenectomy for congenital hemolytic anemia","volume":"51","author":"BR Englum","year":"2016","journal-title":"Journal of pediatric surgery."},{"issue":"1","key":"pcbi.1012705.ref080","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1515\/med-2019-0054","article-title":"Indications and outcomes of splenectomy for hematological disorders","volume":"14","author":"R Ciftciler","year":"2019","journal-title":"Open Medicine."},{"issue":"3","key":"pcbi.1012705.ref081","first-page":"181","article-title":"The role of spleen in suppressing the rheological alterations in circulating blood","volume":"20","author":"OK Baskurt","year":"1999","journal-title":"Clinical Hemorheology and Microcirculation."},{"key":"pcbi.1012705.ref082","doi-asserted-by":"crossref","unstructured":"Lanotte L, Mauer J, Mendez S, Fedosov DA, Fromental JM, Claveria V, et al. Red cells\u2019 dynamic morphologies govern blood shear thinning under microcirculatory flow conditions. Proceedings of the National Academy of Sciences. 2016;113(47):13289\u201313294.","DOI":"10.1073\/pnas.1608074113"},{"key":"pcbi.1012705.ref083","first-page":"263","article-title":"Rheological effects of red blood cell aggregation in the venous network: a review of recent studies","volume":"38","author":"JJ Bishop","year":"2001","journal-title":"Biorheology."},{"issue":"17","key":"pcbi.1012705.ref084","doi-asserted-by":"crossref","first-page":"9726","DOI":"10.1111\/jcmm.15534","article-title":"Effects of sphingolipids overload on red blood cell properties in Gaucher disease","volume":"24","author":"L Dupuis","year":"2020","journal-title":"J Cell Molecul Med."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012705","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012705","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:55:56Z","timestamp":1757958956000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012705"}},"subtitle":[],"editor":[{"given":"Feilim","family":"Mac Gabhann","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":84,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012705","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.10.627687","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]}}}