Microfluidic Modeling of Cell−Cell Interactions in Malaria Pathogenesis

Antia, Meher; Herricks, Thurston; Rathod, Pradipsinh K.

doi:10.1371/journal.ppat.0030099

Cited by 75 publications

(102 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During these steps, Pf-RBCs undergo large membrane deformations as illustrated in the plot and in Movie S2. Similar flipping behavior and large membrane deformations (including membrane buckling) were also found in the experiments (8).…”

Section: Resultssupporting

confidence: 85%

“…Fig. 4 (lower left) presents the average rolling velocity of Pf-RBCs compared with experiments of cell rolling on a surface coated with purified ICAM-1 (8). The simulated average velocities show a near-linear dependence on the shear stress, and are in good agreement with the experiments.…”

Section: Resultssupporting

confidence: 61%

“…However, in the experiments of ref. 8 Pf-RBCs moved on a surface coated with purified ICAM-1 showing persistent and stable rolling over long observation times for a wide range of WSS between 0.2 Pa and 2 Pa. This observation suggests a stabilizing mechanism for the rolling of Pf-RBCs at high shear stresses.…”

Section: Resultsmentioning

confidence: 77%

“…This adherence of Pf-RBCs is believed to be the main cause of bleeding complications in cerebral malaria due to blockages of small vessels in the brain (7). Unlike the extensive research on leukocytes, very few in vitro experiments (8)(9)(10)(11) have examined the adhesive dynamics of Pf-RBCs. For example, in ref.…”

mentioning

confidence: 99%

“…For example, in ref. 8 the walls of microfluidic channels were coated with purified protein ligands participating in cytoadherence (e.g., ICAM-1) and with mammalian Chinese hamster ovary (CHO) cells expressing such ligands. Purified ICAM-1 caused rolling or flipping of Pf-RBCs without detachment or arrest of RBC motion.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation

Fedosov

Caswell

Suresh

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

170

141

View full text Add to dashboard Cite

The pathogenicity of Plasmodium falciparum (Pf) malaria results from the stiffening of red blood cells (RBCs) and its ability to adhere to endothelial cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three-dimensional mesoscopic simulations of flow in cylindrical capillaries in order to predict the flow resistance enhancement at different parasitemia levels. In addition, the adhesive dynamics of Pf-RBCs is explored for various parameters revealing several types of cell dynamics such as firm adhesion, very slow slipping along the wall, and intermittent flipping. The parasite inside the RBC is modeled explicitly in order to capture phenomena such as "hindered tumbling" motion of the RBC and the sudden transition from firm RBC cytoadherence to flipping on the endothelial surface. These predictions are in quantitative agreement with recent experimental observations, and thus the three-dimensional modeling method presented here provides new capabilities for guiding and interpreting future in vitro and in vivo studies of malaria.adhesion | erythrocyte | malaria | mechanical properties | dissipative particle dynamics R ed blood cells parasitized by Plasmodium falciparum (Pf-RBCs) undergo irreversible changes in structure and biophysical characteristics, which can lead to drastically altered blood circulation. The membrane shear modulus of infected RBCs may increase up to ten-fold causing capillary occlusions (1, 2), thereby resulting in substantial increase in resistance to blood flow. Such effects may be intensified due to the enhanced cytoadherence of Pf-RBCs to the vascular endothelium (3-6). This adherence of Pf-RBCs is believed to be the main cause of bleeding complications in cerebral malaria due to blockages of small vessels in the brain (7). Unlike the extensive research on leukocytes, very few in vitro experiments (8-11) Recent progress in multiscale numerical modeling (12-14) allows us to model soft matter, and RBCs in particular, at sufficient detail, i.e., simulating nanometer scales while simultaneously capturing the large scale dynamics. We have developed and validated a Dissipative Particle Dynamics (DPD) model (12, 14-16) that can accurately simulate the properties and dynamic behavior of healthy RBCs as well as Pf-RBCs. The multiscale model can represent a RBC at the spectrin level with 30,000 points (17) or at a coarser level with 500 points by proper scaling of the physiologically correct parameters (12, 14, 15); hence, no ad hoc calibration is required. The predictive capability of the DPD model has been demonstrated in comparisons with microfluidic experiments that probe controlled pressure-velocity relationships of (healthy) RBC flow through microchannels whose inner openings mimic the smallest dimensions for RBC passage in the microvasculature (16). In addition, we have extended the adhesive dynamics model of (18,19) to the DPD framework, and validated it by simulating the adhesive dynamics of leukocytes for which extensive experimental results exist (20,21). In summary, ...

show abstract

Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 77%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation

Fedosov

Caswell

Suresh

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

170

141

View full text Add to dashboard Cite

show abstract

Modeling cytoadhesion of Plasmodium falciparum‐infected erythrocytes and leukocytes—common principles and distinctive features

et al. 2016

View full text Add to dashboard Cite

Cytoadhesion of Plasmodium falciparum‐infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. In both cases, adhesins are presented in structures that raise them above the cell surface. Another similarity is the enhancement of adhesion under physical force (catch bonding). Here, we review recent advances in our understanding of the molecular and biophysical mechanisms underlying cytoadherence in both cellular systems. We describe how imaging, flow chamber experiments, single‐molecule measurements, and computational modeling have been used to decipher the relevant processes. We conclude that although the parasite seems to induce processes that resemble the cytoadherence of leukocytes, the mechanics of erythrocytes is such that the resulting behavior in shear flow is fundamentally different.

show abstract

Dissipative Particle Dynamics

Pivkin

Caswell

Karniadakisa

2010

Reviews in Computational Chemistry

View full text Add to dashboard Cite

Dissipative Particle Dynamics (DPD) is a mesoscopic simulation method, potentially very effective in simulating mesoscale hydrodynamics and soft matter. This thesis addresses open theoretical and algorithmic questions of DPD and demonstrates the new developments with applications to blood flow in health as well as in sickle cell anemia. The first part investigates the intrinsic relation of DPD to the microscopic Molecular Dynamics (MD) method through the Mori-Zwanzig theory. We provide a physical explanation for the dissipative and random forces by constructing a mesoscopic system directly from a microscopic one. The relationship between DPD and MD is quantified and the many-body effect on the hydrodynamics of the coarsegrained system is discussed. We then address algorithmic issues and develop a simple approach for imposing proper no-slip boundary conditions for wall-bounded fluid systems and outflow boundary conditions for open fluid systems. The second part deals with blood flow applications. First, we use DPD and multi-scale red blood cell models to investigate the transition of blood flow from Newtonian to non-Newtonian behavior as the arteriole size decreases. Then, we develop a multi-scale model for the sickle red blood cells (RBCs), accounting for diversity in shapes and polymerization of hemoglobin. Subsequently, we use this model to investigate abnormal rheology and hemodynamics of the sickle blood flow under different physiological conditions.Despite the increased flow resistance, no occlusion was observed in a straight tube under any conditions unless an adhesive dynamics model was explicitly incorporated into our simulations. This new adhesion model includes both sickle RBCs as well as leukocytes. The former interact with the vascular endothelium, with the deformable sickle cells (SS2) exhibiting larger adhesion. The adherent SS2 cells further trap rigid irreversible sickle cells (SS4) resulting in vaso-occlusion in vessels less than 15µm. Under inflammation, adherent leukocytes may also trap SS4 cells resulting in vaso-occlusion in even larger vessels.

show abstract

Microfluidic Modeling of Cell−Cell Interactions in Malaria Pathogenesis

Cited by 75 publications

References 57 publications

Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation

Quantifying the biophysical characteristics of Plasmodium-falciparum -parasitized red blood cells in microcirculation

Modeling cytoadhesion of Plasmodium falciparum‐infected erythrocytes and leukocytes—common principles and distinctive features

Dissipative Particle Dynamics

Contact Info

Product

Resources

About