Cell adhesion during bullet motion in capillaries

Takeishi, Naoki; Imai, Yohsuke; Ishida, Shunichi; Omori, Toshihiro; Kamm, Roger D.; Ishikawa, Takuji

doi:10.1152/ajpheart.00241.2016

Cited by 34 publications

(60 citation statements)

References 64 publications

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“…All procedures were fully implemented on graphics processing unit (GPU) to accelerate the numerical simulation 54 . Our coupling method has been successfully applied to numerical analyses of leukocytes 43 , circulating tumor cells 55 and cell adhesion 56 . The solid and fluid mesh sizes were set to be 250 nm (an unstructured mesh with 5,120 elements was used for the RBC membrane and 1,280 elements for the MP membrane).…”

Section: Methodsmentioning

confidence: 99%

Capture of microparticles by bolus flow of red blood cells in capillaries

Takeishi

Imai

2017

Sci Rep

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Previous studies have concluded that microparticles (MPs) can more effectively approach the microvessel wall than nanoparticles because of margination. In this study, however, we show that MPs are not marginated in capillaries where the vessel diameter is comparable to that of red blood cells (RBCs). We numerically investigated the behavior of MPs with a diameter of 1 μm in various microvessel sizes, including capillaries. In capillaries, the flow mode of RBCs shifted from multi-file flow to bolus (single-file) flow, and MPs were captured by the bolus flow of the RBCs instead of being marginated. Once MPs were captured, they rarely escaped from the vortex-like flow structures between RBCs. These capture events were enhanced when the hematocrit was decreased, and reduced when the shear rate was increased. Our results suggest that microparticles may be rather inefficient drug carriers when targeting capillaries because of capture events, but nanoparticles, which are more randomly distributed in capillaries, may be more effective carriers.The flow behavior of microparticles (MPs) is of paramount importance in drug delivery systems targeting capillary districts 1-3 . The behavior of MPs in the microcirculation, therefore, has been widely studied over decades 3,4 . MPs in blood are subject to hydrodynamic interaction with red blood cells (RBCs), which exhibit axial migration, resulting in MPs appearing primarily in the peripheral layer. This is termed margination, which is the first step in the adhesion of circulating particles to the endothelium. The behavior of platelets has been investigated in in vivo experiments using rabbit mesentery, looking at arterioles 5 and venules 6 with vessel diameters ranging from 15 to 35 μm. The effects of physical conditions (e.g., shear rate) on margination have been systematically investigated using glass tubes 7 and PDMS channels 8 . These studies provided insight not only into microcirculatory blood flow but also into therapeutic drug carriers. In vitro experiments were performed to determine the optimal size/shape of drug carriers to effectively adhere to the vascular wall 9, 10 . For example, Charoenphol et al. showed that microspheres (1-10 μm in diameter) more efficiently adhered to the endothelium in microchannels than nanoparticles (≤500 nm in diameter) in blood flow 9 .Numerical simulations have been also performed to investigate the margination of MPs 11-18 . Müller et al. 12 investigated the effect of the particle size/shape, shear rate, channel width, and volume fraction of RBCs (hematocrit, Hct) on margination. Their two-dimensional model showed that large particles (1.83 μm or 0.91 μm in diameter) more efficiently marginated than small particles (0.25 μm in diameter) for various shear rates 12 . Some of the experimental results of MP margination were discussed with numerical results 19,20 . Lee et al. 20 , for example, demonstrated that nanoparticles (200 nm in diameter) randomly distributed in postcapillary venules with a diameter ranging from 15-30 μm, while micro...

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Section: Methodsmentioning

confidence: 99%

Capture of microparticles by bolus flow of red blood cells in capillaries

Takeishi

Imai

2017

Sci Rep

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“…Our methods are validated for different viscosity ratios by comparing the values of the Taylor parameter of deformed spherical capsules with those reported in Foessel et al (2011), as detailed in the appendix §A.1. A volume constraint is implemented to counteract the accumulation of small errors in the volume of the individual cells (Freund 2007): in our simulation, the volume error is always maintained lower than 1.0×10 −3 %, as tested and validated in our previous study on cell adhesion (Takeishi et al 2016). All numerical procedures are fully implemented on graphics processing unit (GPU) to accelerate the numerical simulation (Miki et al 2012).…”

Section: )mentioning

confidence: 99%

Haemorheology in dilute, semi-dilute and dense suspensions of red blood cells

et al. 2019

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We present a numerical analysis of the rheology of a suspension of red blood cells (RBCs) in a wall-bounded shear flow. The flow is assumed as almost inertialess. The suspension of RBCs, modeled as biconcave capsules whose membrane follows the Skalak constitutive law, is simulated for a wide range of viscosity ratios between the cytoplasm and plasma: λ = 0.1-10, for volume fractions up to φ = 0.41 and for different capillary numbers (Ca). Our numerical results show that an RBC at low Ca tends to orient to the shear plane and exhibits the so-called rolling motion, a stable mode with higher intrinsic viscosity than the so-called tumbling motion. As Ca increases, the mode shifts from the rolling to the swinging motion. Hydrodynamic interactions (higher volume fraction) also allows RBCs to exhibit both tumbling or swinging motions resulting in a drop of the intrinsic viscosity for dilute and semi-dilute suspensions. Because of this mode change, conventional ways of modeling the relative viscosity as a polynomial function of φ cannot be simply applied in suspensions of RBCs at low volume fractions. The relative viscosity for high volume fractions, however, can be well described as a function of an effective volume fraction, defined by the volume of spheres of radius equal to the semi-middle axis of the deformed RBC. We find that the relative viscosity successfully collapses on a single non-linear curve independently of λ except for the case with Ca 0.4, where the fit works only in the case of low/moderate volume fraction, and fails in the case of a fully dense suspension.

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“…If this diameter is comparable or smaller than that of the cell itself, the cells are not rolling as observed in venules but due to the small diameter they are travelling with a bullet motion. Under these circumstances the P-selectin-PSGL-1 interaction is not a weak interaction anymore but can provide a firm adherence to the wall of the capillary [42]. …”

Section: Role Of Selectins and Psgl-1 In Physiological Leukocyte Rmentioning

confidence: 99%

The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression

Kappelmayer

Nagy

2017

BioMed Research International

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Cellular interaction is inevitable in the pathomechanism of human disease. Formation of heterotypic cellular aggregates, between distinct cells of hematopoietic and nonhematopoietic origin, may be involved in events leading to inflammation and the complex process of cancer progression. Among adhesion receptors, the family of selectins with their ligands have been considered as one of the major contributors to cell-cell interactions. Consequently, the inhibition of the interplay between selectins and their ligands may have potential therapeutic benefits. In this review, we focus on the current evidence on the selectins as crucial modulators of inflammatory, thrombotic, and malignant disorders. Knowing that there is promiscuity in selectin binding, we outline the importance of a key protein that serves as a ligand for all selectins. This dimeric mucin, the P-selectin glycoprotein ligand 1 (PSGL-1), has emerged as a major player in inflammation, thrombus, and cancer development. We discuss the interaction of PSGL-1 with various selectins in physiological and pathological processes with particular emphasis on mechanisms that lead to severe disease.

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Cell adhesion during bullet motion in capillaries

Cited by 34 publications

References 64 publications

Capture of microparticles by bolus flow of red blood cells in capillaries

Capture of microparticles by bolus flow of red blood cells in capillaries

Haemorheology in dilute, semi-dilute and dense suspensions of red blood cells

The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression

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