Quantifying the rheological and hemodynamic characteristics of sickle cell anemia.

Sickle erythrocytes exhibit abnormal morphology and membrane mechanics under deoxygenated conditions due to the polymerization of hemoglobin S. We employed dissipative particle dynamics to extend a validated multiscale model of red blood cells (RBCs) to represent different sickle cell morphologies based on a simulated annealing procedure and experimental observations. We quantified cell distortion using asphericity and elliptical shape factors, and the results were consistent with a medical image analysis. We then studied the rheology and dynamics of sickle RBC suspensions under constant shear and in a tube. In shear flow, the transition from shear-thinning to shear-independent flow revealed a profound effect of cell membrane stiffening during deoxygenation, with granular RBC shapes leading to the greatest viscosity. In tube flow, the increase of flow resistance by granular RBCs was also greater than the resistance of blood flow with sickle-shape RBCs. However, no occlusion was observed in a straight tube under any conditions unless an adhesive dynamics model was explicitly incorporated into simulations that partially trapped sickle RBCs, which led to full occlusion in some cases.

[1]  R. Nagel,et al.  Erythrocytes in sickle cell anemia are heterogeneous in their rheological and hemodynamic characteristics. , 1983, The Journal of clinical investigation.

[2]  S. Chien,et al.  Effect of deoxygenation on blood rheology in sickle cell disease. , 1975, Microvascular research.

[3]  George Em Karniadakis,et al.  Direct construction of mesoscopic models from microscopic simulations. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[4]  M. Fabry,et al.  In Vivo Studies of Sickle Red Blood Cells , 2004, Microcirculation.

[5]  J. Hofrichter,et al.  Kinetics of sickle hemoglobin polymerization. II. A double nucleation mechanism. , 1985, Journal of molecular biology.

[6]  P. Español,et al.  FLUID PARTICLE MODEL , 1998 .

[7]  Gerhard Gompper,et al.  Predicting human blood viscosity in silico , 2011, Proceedings of the National Academy of Sciences.

[8]  George Em Karniadakis,et al.  Wall shear stress-based model for adhesive dynamics of red blood cells in malaria. , 2011, Biophysical journal.

[9]  S Chien,et al.  Effects of hemoglobin concentration on deformability of individual sickle cells after deoxygenation. , 1995, Blood.

[10]  W. Helfrich.  Elastic Properties of Lipid Bilayers: Theory and Possible Experiments , 1973, Zeitschrift fur Naturforschung. Teil C: Biochemie, Biophysik, Biologie, Virologie.

[11]  Ian Halliday,et al.  Lattice Boltzmann modelling of blood cell dynamics , 2008 .

[12]  J. Hofrichter,et al.  Kinetics of sickle hemoglobin polymerization. I. Studies using temperature-jump and laser photolysis techniques. , 1985, Journal of molecular biology.

[13]  P. B. Warren,et al.  DISSIPATIVE PARTICLE DYNAMICS : BRIDGING THE GAP BETWEEN ATOMISTIC AND MESOSCOPIC SIMULATION , 1997 .

[14]  Subra Suresh,et al.  Molecularly based analysis of deformation of spectrin network and human erythrocyte , 2006 .

[15]  M. S. Turner,et al.  Stall, spiculate, or run away: The fate of fibers growing towards fluctuating membranes. , 2006, Physical review letters.

[16]  J. Koelman,et al.  Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics , 1992 .

[17]  Robin W. Briehl,et al.  Nucleation and growth of fibres and gel formation in sickle cell haemoglobin , 1990, Nature.

[18]  D. Hammer,et al.  Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. , 1992 .

[19]  L. Pauling,et al.  Sickle cell anemia a molecular disease. , 1949, Science.

[20]  T Asakura,et al.  Morphologic studies of sickle erythrocytes by image analysis. , 1990, The Journal of laboratory and clinical medicine.

[21]  A. Schechter,et al.  Influence of sickle hemoglobin polymerization and membrane properties on deformability of sickle erythrocytes in the microcirculation. , 1992, Biophysical journal.

[22]  A Leung,et al.  Static and dynamic rigidities of normal and sickle erythrocytes. Major influence of cell hemoglobin concentration. , 1984, The Journal of clinical investigation.

[23]  L Mahadevan,et al.  Sickle cell vasoocclusion and rescue in a microfluidic device , 2007, Proceedings of the National Academy of Sciences.

[24]  William A Eaton,et al.  Understanding the shape of sickled red cells. , 2005, Biophysical journal.

[25]  S. Edwards,et al.  The computer study of transport processes under extreme conditions , 1972 .

[26]  F F Costa,et al.  Optical tweezers for measuring red blood cell elasticity: application to the study of drug response in sickle cell disease , 2003, European journal of haematology.

[27]  George Em Karniadakis,et al.  Accurate coarse-grained modeling of red blood cells. , 2008, Physical review letters.

[28]  Daniel T Chiu,et al.  A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Mattiello,et al.  Partially oxygenated sickled cells: sickle-shaped red cells found in circulating blood of patients with sickle cell disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D K Kaul,et al.  Rate of deoxygenation and rheologic behavior of blood in sickle cell anemia. , 1991, Blood.

[31]  X. Liu,et al.  Rate of deoxygenation modulates rheologic behavior of sickle red blood cells at a given mean corpuscular hemoglobin concentration. , 1999, Clinical hemorheology and microcirculation.

[32]  D. Boal,et al.  Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration. , 1998, Biophysical journal.

[33]  George Em Karniadakis,et al.  A multiscale red blood cell model with accurate mechanics, rheology, and dynamics. , 2010, Biophysical journal.

[34]  P. Español,et al.  Statistical Mechanics of Dissipative Particle Dynamics. , 1995 .

[35]  S. Lowen.  The Biophysical Journal , 1960, Nature.

[36]  R. Nagel,et al.  Erythrocytic and Vascular Factors Influencing the Microcirculatory Behavior of Blood in Sickle Cell Anemia a , 1989, Annals of the New York Academy of Sciences.

[37]  B. Coller,et al.  Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm , 2002, Proceedings of the National Academy of Sciences of the United States of America.