Deformation of a red blood cell in a narrow rectangular microchannel

The deformability of a red blood cell (RBC) is one of the most important biological parameters affecting blood flow, both in large arteries and in the microcirculation, and hence it can be used to quantify the cell state. Despite numerous studies on the mechanical properties of RBCs, including cell rigidity, much is still unknown about the relationship between deformability and the configuration of flowing cells, especially in a confined rectangular channel. Recent computer simulation techniques have successfully been used to investigate the detailed behavior of RBCs in a channel, but the dynamics of a translating RBC in a narrow rectangular microchannel have not yet been fully understood. In this study, we numerically investigated the behavior of RBCs flowing at different velocities in a narrow rectangular microchannel that mimicked a microfluidic device. The problem is characterized by the capillary number Ca, which is the ratio between the fluid viscous force and the membrane elastic force. We found that confined RBCs in a narrow rectangular microchannel maintained a nearly unchanged biconcave shape at low Ca, then assumed an asymmetrical slipper shape at moderate Ca, and finally attained a symmetrical parachute shape at high Ca. Once a RBC deformed into one of these shapes, it was maintained as the final stable configurations. Since the slipper shape was only found at moderate Ca, measuring configurations of flowing cells will be helpful to quantify the cell state.Takeishi, Naoki, Hiroaki Ito, Makoto Kaneko, and Shigeo Wada. 2019. "Deformation of a Red Blood Cell in a Narrow Rectangular Microchannel" Micromachines 10, no. 3: 199. https://doi.org/10.3390/mi1003019

Haemorheology of dense suspension of red blood cells under oscillatory shear flow

We present a numerical analysis of the rheology of a suspension of red blood cells (RBCs) for different volume fractions in a wall-bounded, effectively inertialess, oscillatory shear flow. The RBCs are modeled as biconcave capsules, whose membrane is an isotropic and hyperelastic material following the Skalak constitutive law, and the suspension examined for a wide range of applied frequencies. The frequency-dependent viscoelasticity in the bulk suspension is quantified by the complex viscosity, defined by the amplitude of the particle shear stress and the phase difference between the stress and shear. Our numerical results show that deformations of RBCs wekaly depend on the shear frequency, and the normal stress differences, membrane tension and amplitude of the shear stress are reduced by the oscillations. The frequency-dependent complex viscosity is nevertheless consistent with the classical behavior of non-Newtonian fluids, where the real part of the complex viscosity $\eta^\prime$ decreases as the frequency increases, and the imaginary part $\eta^{\prime\prime}$ exhibit a maximum value at an intermediate frequency. Such local maximum frequency is the same in both dense and dilute conditions. The effect of the viscosity ratios between the cytoplasm and plasma, volume fractions of RBCs, and oscillatory amplitudes represented by a capillary number on the complex viscosity are also assessed

Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formation

Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. It is theorized that the mechanical effect of the fibrin clot is caused by the polymeric protofibrils between crosslinks, or to their dynamics on a nanoscale order. Despite a number of studies, however, it is still unknown, how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. A mesoscopic framework would be useful to tackle this multi-scale problem, but it has not yet been established. We thus propose a minimal mesoscopic model for protofibrils based on Brownian dynamics, and performed numerical simulations of protofibril aggregation. We also performed stretch tests of polymeric protofibrils to quantify the elasticity of fibrin clots. Our model results successfully captured the conformational properties of aggregated protofibrils, e.g., strain-hardening response. Furthermore, the results suggest that the bending stiffness of individual protofibrils increases to resist extension.Takeishi Naoki, Shigematsu Taiki, Enosaki Ryogo, Ishida Shunichi, Ii Satoshi and Wada Shigeo 2021Development of a mesoscopic framework spanning nanoscale protofibril dynamics to macro-scale fibrin clot formationJ. R. Soc. Interface.182021055420210554 http://doi.org/10.1098/rsif.2021.055

Deformation of a Red Blood Cell in a Narrow Rectangular Microchannel

The deformability of a red blood cell (RBC) is one of the most important biological parameters affecting blood flow, both in large arteries and in the microcirculation, and hence it can be used to quantify the cell state. Despite numerous studies on the mechanical properties of RBCs, including cell rigidity, much is still unknown about the relationship between deformability and the configuration of flowing cells, especially in a confined rectangular channel. Recent computer simulation techniques have successfully been used to investigate the detailed behavior of RBCs in a channel, but the dynamics of a translating RBC in a narrow rectangular microchannel have not yet been fully understood. In this study, we numerically investigated the behavior of RBCs flowing at different velocities in a narrow rectangular microchannel that mimicked a microfluidic device. The problem is characterized by the capillary number C a , which is the ratio between the fluid viscous force and the membrane elastic force. We found that confined RBCs in a narrow rectangular microchannel maintained a nearly unchanged biconcave shape at low C a , then assumed an asymmetrical slipper shape at moderate C a , and finally attained a symmetrical parachute shape at high C a . Once a RBC deformed into one of these shapes, it was maintained as the final stable configurations. Since the slipper shape was only found at moderate C a , measuring configurations of flowing cells will be helpful to quantify the cell state

Successful Revascularization to Right Coronary Artery by Percutaneous Coronary Intervention after Endovascular Therapy for Leriche Syndrome

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patient's symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome

The unfolded protein response is activated in Helicobacter-induced gastric carcinogenesis in a non-cell autonomous manner

Mucous metaplasia (MM) is an aberrant secretory phenotype that arises during Helicobacter-induced gastric carcinogenesis. HSPA5, a key modulator of the unfolded protein response (UPR) activated by endoplasmic reticulum (ER) stress is overexpressed in gastric cancer (GC). We studied activation of the UPR in MM and GC in humans and mice. We assessed RNA and protein levels of ER stress markers (HSPA5, XBP1, and CHOP) in human GC, and correlated with Helicobacter pylori (H. pylori) status, then surveyed HSPA5 in normal gastric mucosa and gastric pre-neoplasia including gastritis and intestinal metaplasia (IM). The role of H. pylori infection in the UPR was assessed by co-culture with AGS GC cells. ER stress markers in metaplasia and dysplasia from transgenic K19-Wnt1/C2mE mice and C57Bl/6 mice with chronic Helicobacter felis (H. felis) infection were compared. HSPA5 was overexpressed in 24/73 (33%) of human GC. Induction of HSPA5 and XBP1 splicing was associated with H. pylori-associated GC (P=0.007 for XBP1 splicing). HSPA5 was overexpressed in MM but not gastritis in patients with H. pylori infection. Stimulation of AGS cells with CagA-positive H. pylori suppressed HSPA5 expression and XBP1 splicing. In the normal gastric mucosa of human and mouse, HSPA5 was constitutively expressed in MIST1-positive chief cells. Increased Hspa5 and Chop expression were found in dysplasia of C57Bl/6 mice with chronic H. felis infection but was absent in spontaneous gastric dysplasia in K19-Wnt1/C2mE mice with concomitant loss of Mist1 expression, similar to that observed in H. pylori-associated human GC. Induction of the UPR in the milieu of Helicobacter-induced chronic inflammation and MM may promote neoplastic transformation of Helicobacter-infected gastric mucosa.This work was supported by grants from the National Health and Medical Research Council (DT), the Canberra Hospital Radiation Oncology Trust Fund (DT), the Canberra Region Medical Foundation (DT), and ESA International (DT)

脳循環と脳脊髄液の流れを統合した動態解析モデル

Objectives:In the fluid dynamics of cerebral circulation and cerebrospinal fluid (CSF) motion, the computational simulation model has not been established. We conducted the multi-scale simulation in the cerebral circulation model. Therefore, we would like to integrate these two different fluid dynamics models.Methods & Results:Using the 3 tesla MRI and 3D workstation, the flow volumes of blood and CSF were measured in the 20 healthy volunteers. In addition, the 3D structures and movements of the brain, intracranial CSF spaces and major arteries were reconstructed for computational fluid dynamics.Conclusions:The CSF movements synchronized with a heartbeat were driven by the pulsation of large intracranial arteries and brain. In the current concepts of the cerebral circulation and fluid exchange of CSF and interstitial fluid, i.e., glymphatic system, the simulation model of the brain fluid dynamic is extremely complicated. There are many black boxes in this field