Narrow Capillaries Research Articles

Promotion of whole blood rheology after vitamin C supplementation: focus on red blood cells 1.

Hemorheological properties represent significant contributors in the pathogenesis of cardiovascular diseases. As plasma vitamin C is inversely associated with blood viscosity in humans, we aimed to characterize the effect of vitamin C supplementation on hemorheology with an emphasis on erythrocyte functions. Twenty young healthy volunteers were asked to take vitamin C (1000 mg per day) for 3 weeks. We observed beneficial effect of intervention on multiple hemorheological parameters: whole blood viscosity in the range of medium to high shear rates, Casson yield stress, complex viscosity, and storage and loss moduli. As erythrocyte properties play a significant role in hemorheology, we characterized their deformability, nitric oxide production, and sodium pump activity in erythrocyte membranes. We can conclude that observed promotion in whole blood rheology may be consequence of improved erythrocyte functionality as concerns their ability to pass through narrow capillaries of the microcirculation, nitric oxide production, and sodium pump activity. Parameters reflecting oxidative stress and antioxidant status in plasma were not affected by our intervention. As improvement in hemorheology may play an important role in cardioprotection, it would be challenging to investigate the vitamin C supplementation to patients suffering from microcirculatory disturbances and worsened organ perfusion in the case of cardiovascular diseases.

Targeting liver sinusoidal endothelial cell activation during angiogenesis using miRNA: a new therapeutic approach against liver metastasis

Colorectal cancer is the third most frequently occurring cancer and a common cause of cancer-related death worldwide (1). The most common metastatic target organ of colorectal cancer is the liver (2). The first interaction between colon cancer cell and liver occurs in the liver sinusoid. The narrow fenestrated capillaries of the hepatic tissue (3). The tumor cell is trapped in this space and start the interaction between metastatic cell and host organ.

Neutrophil Cell Shape Change: Mechanism and Signalling during Cell Spreading and Phagocytosis.

Perhaps the most important feature of neutrophils is their ability to rapidly change shape. In the bloodstream, the neutrophils circulate as almost spherical cells, with the ability to deform in order to pass along narrower capillaries. Upon receiving the signal to extravasate, they are able to transform their morphology and flatten onto the endothelium surface. This transition, from a spherical to a flattened morphology, is the first key step which neutrophils undergo before moving out of the blood and into the extravascular tissue space. Once they have migrated through tissues towards sites of infection, neutrophils carry out their primary role—killing infecting microbes by performing phagocytosis and producing toxic reactive oxygen species within the microbe-containing phagosome. Phagocytosis involves the second key morphology change that neutrophils undergo, with the formation of pseudopodia which capture the microbe within an internal vesicle. Both the spherical to flattened stage and the phagocytic capture stage are rapid, each being completed within 100 s. Knowing how these rapid cell shape changes occur in neutrophils is thus fundamental to understanding neutrophil behaviour. This article will discuss advances in our current knowledge of this process, and also identify an important regulated molecular event which may represent an important target for anti-inflammatory therapy.

Microfluidic assemblies designed for assessment of drug effects on deformability of human erythrocytes

Extreme deformability of human erythrocytes is a prerequisite for their ability to squeeze through narrow capillaries of the blood microcirculation system. Various drugs can modify this deformability and consequently provoke circulation problems. We demonstrate that microfluidic assemblies are very convenient platforms for in vitro study of the associated processes. Two types of microfluidic channels were designed to quantitatively investigate modifications of erythrocyte deformability induced by hydrogen peroxide, ethanol and pentoxifylline based on transit velocity measurements. With a high sensitivity our microfluidic assemblies show that hydrogen peroxide decreases erythrocyte deformability in a dose-dependent manner. Then, results on ethanol resolve a biphasic nature of this reactant on the deformability of single erythrocyte cells. Results on pentoxifylline provide evidence that, similar to ethanol, also this medical drug has a double-sided effect on the erythrocyte deformability, i.e. increasing the deformability at low concentrations, while decreasing it at higher ones. Taken together, our microfluidic designs propose a potent measurement method for the erythrocyte deformability, as well as providing a perspective to evaluate effects of drugs on it.

Fabrication of 3D microchannels for tissue engineering in photosensitive glass using NIR femtosecond laser radiation

Abstract The biocompatibility of photosensitive glasses allows various biomedical applications; one is the field of tissue engineering and more precisely microengineered tissue-on-a-chip platforms to study the tissue microenvironment and disease modelling. Three dimensional architectures of adapted components are required for modern materials. A photosensitive lithiumalumosilicate glass FS21 was investigated regarding the interaction with a Ti:Sapphire laser systemto build three dimensional buried channels inside the glass. Femtosecond laser radiation with a wavelength of 800 nm and pulse duration of 140 fs was used to modify the glass structure. Subsurface channel geometries were achieved by a subsequent thermal treatment and were formed into capillaries using wet chemical etching of the exposed and crystallised channels. Contrary to ultraviolet (UV) exposure, spectral optical investigations showed that fs laser exposure caused various radiation induced defects in the base glass coupled with the generation of photoelectrons for the photochemical modification of silver ions. We observed an outgassing of different species coming from raw materials of the original glass batch during the glass crystallisation process. Etch rate ratios differ between 1:25 and 1:45 and are dependent on: stoichiometric deviation between surface and bulk, crystal size and distribution and exchange of the etching agent in narrow capillaries.

Peak sharpening limits of solvent-assisted post-column refocusing to enhance detection limits in liquid chromatography

We report on a numerical and experimental study of the limits of peak refocusing and concentration enhancement that can be obtained with solvent front-assisted peak remobilization in a trap column receiving peaks eluting from a preceding analytical column. It is shown that the upper limit of peak refocusing can best be pursued by injecting a sufficiently large volume in a sufficiently narrow capillary and elute it with a sufficiently steep (ballistic) gradient. Corresponding equations offering a quantitative description have been derived and verified experimentally. For the latter purpose, peak volumes of the order of 0.5 to 2.0 μL were refocused in a dedicated set-up capable of trapping μL-sized peaks in a 75 μm i.d. capillary and remobilized using a nano-LC pump propelling an acetonitrile/isopropyl alcohol mixture with a viscosity matching that of the trapping solvent. Injecting 2.0 μL peaks, a peak refocusing factor of 17.3 could be achieved.

Inhibitory Effect of a Novel DNA Aptamer with Artificial Nucleic Bases for Von Willebrand Factor A1 Domain on Platelet Thrombosis Formation

<Introduction>von Willebrand factor (VWF) is a blood glycoprotein that plays an important role in platelet thrombus formation through interaction with its A1 domain and platelet glycoprotein 1b. Thus, VWF A1 domain was thought to be a good therapeutic target candidate for VWF mediated thrombosis. In this study, we analyzed the inhibitory effects of a novel DNA aptamer (TAGX-0004) on platelet aggregation compared with another VWF A1 domain binding aptamer (ARC1779) which had entered to Phase II clinical trial for acquired thrombotic thrombocytopenic purpura (TTP) in 2011.<Methods>TAGX-0004 was generated by SELEX (systematic evolution of ligands by exponential enrichment) and consisted of artificial nucleic acid base, 7-(2-thienyl) imidazo [4,5-b] pyridine (Ds) as well as natural bases (Adenine, Thymine, Cytosine and Guanine). The dissociation constant (Kd) of the aptamers was analyzed by electrophoretic mobility shift assay (EMSA). 100 nM of each DNA aptamer was mixed with A1 domain of VWF protein (final concentration was 0 to 800 nM) in binding buffer (1x PBS, 0.005% NP-40) and incubated for 30 min at 37 °C. The samples were subjected to EMSA with 8% native PAGE, then stained by SYBR Gold. Kd value was determined with scatchard plot analysis. To characterize the binding sites of VWF A1 to these DNA aptamers, various mutants of VWF A1 domain were generated with an alanine substitution technique.Platelet aggregation was induced with ristocetin (RIPA), botrocetin (BIPA), collagen, epinephrine and adenosine diphosphate (ADP). The change of light transmission rate of platelet rich plasma (PRP) compared to platelet poor plasma (PPP) at 37 °C was recorded for 6 min, then the inhibition ratio of platelet aggregation was determined. Total thrombus-formation analysis system (T-TAS) (Fujimori Kogyo Co. Ltd., Tokyo, Japan), which is a novel micro-chip flow-chamber system, was employed to analyze thrombus formation visually and quantitatively in whole blood samples. The micro-chip coated with type 1 collagen was used for this analysis. Anti-VWF A1 inhibitory effects of these aptamers at high shear stress (initial rate of 2000 s-1) were calculated by continuous pressure levels within its narrow capillary. The course of thrombus formation was also optically recorded with a video-microscope located under the microchip.<Results>Biophysical interaction analysis using EMSA showed that TAGX-0004 had approximately 15-times higher binding activity to VWF A1 domain than ARC1779. Based on an alanine scan analysis, it was revealed that a couple of residues we tested were critical for binding of ARC1779 but not for TAGX-0004, which indicating that TAGX-0004 interacts with VWF A1 domain via different amino acid residue(s).Both aptamers did not inhibit the platelet aggregation induced by collagen, epinephrine or ADP. In RIPA, the 80% inhibition was observed by TAGX-0004 and ARC1779 at a final concentration of 10 nM and 750 nM, respectively. In BIPA, those were seen at those of 50 nM and 1000 nM, respectively. In T-TAS analysis, TAGX-0004 inhibited the thrombus formation completely at a final concentration of 100 nM, whereas ARC1779 exhibited partial inhibition of thrombosis formation even at 1000 nM. These results indicated that TAGX-0004 had stronger inhibitory effect on the platelet aggregation compared with ARC1779 under both static and high-shear conditions.<Conclusions>In the present study, we showed the affinity to VWF-A1 domain of TAGX-0004 was stronger than that of ARC1779. In addition, TAGX-0004 was more effective in suppressing platelet aggregation under both static and high-shear stress condition than ARC1779. In the published results of clinical study of ARC1779, there were no hemorrhagic complications in the small clinical trial of patients (7 patients of ARC1779 group) despite the almost complete suppression of VWF function in severely thrombocytopenic patients. Therefore, TAGX-0004 could be developed as a promising therapeutic agent for VWF mediated thrombotic disorders, such as acute coronary syndrome and TTP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of Phenotype-Genotype Correlation in Two Common PIEZO1 Mutations p.R2456H and p.L2495_E2495dup

Hereditary xerocytosis (HX) is a rare autosomal dominant hemolytic anemia caused by mutations in the mechanosensitive cation channel PIEZO1 or, less commonly, in the Ca2+-gated K+ channel KCNN4 (Gardos channel). It is a clinically heterogeneous condition, characterized by erythrocyte dehydration. As erythrocytes traverse narrow capillaries and sinusoids, PIEZO1 is thought to be activated by mechanical stimuli, leading to increased intracellular Ca2+ which then may activate KCNN4, causing K+ efflux and water loss. The p.R2456H and p.L2495_E2496dup PIEZO1 mutations are likely the most common of the PIEZO1 disease-causing mutations and both result in delayed channel inactivation (Glogowska et al., 2017, Blood 130:1845). The prolonged channel activity in response to mechanical stimulation is likely to contribute to erythrocyte dehydration.Ten patients with PIEZO1-associated HX (5 with p.R2456H and 5 with p.L2495_E2496dup PIEZO1 heterozygous mutations) had their diagnosis established utilizing a Next Generation sequencing panel for hereditary hemolytic and congenital dyserythropoietic anemias (HHA/CDA panel). These patients, along with family members who had similar clinical characteristics (a total of 8 patients with p.R2456H and 6 patients with p.L2495_E2496dup) ranging from 2 - 63 years of age, were enrolled in an IRB-approved study to explore the phenotype-genotype correlation of the disease. We collected patient and family histories and laboratory data and performed phenotypic testing including ektacytometry and erythrocyte cation determinations by atomic spectroscopy.Most of the patients in our cohort had compensated hemolysis without anemia at the time of evaluation and had not required any transfusions. All of the patients had elevated reticulocyte counts ranging from 5.7 to 15.7 %. Reticulocyte counts of individuals with the p.R2456H mutation were significantly higher than those with the p.L2495_E2496dup mutation (Student's t test, p=0.01). Some of the patients had splenomegaly, but it was not a universal finding. Although elevated MCHC is often considered a hallmark of HX, most of the individuals in this cohort had increased MCV and MCH but only high-normal MCHC. Varying percentages of hyper dense cells were detected in blood samples analyzed using an Advia Hematology System and stomatocytes were notable in most peripheral blood smears.Several complications have been associated with HX including hydrops fetalis, hemolytic episodes, thrombosis (especially after splenectomy), gallstones, and iron overload. One patient in our cohort had experienced ascites and a pleural effusion in the perinatal period and one was diagnosed with gallstones at age 11. Nearly all the patients had an increase in total bilirubin. Ferritin levels were increased in the majority of the patients tested after 15 years of age. The three patients older than 40 years of age had iron overload verified by T2* MRI imaging of the liver.HX presents several diagnostic challenges due to its heterogeneity. Two of the subjects in our study had been previously diagnosed with hereditary spherocytosis (HS) and one had the diagnosis of congenital dyserythropoietic anemia (CDA) prior to genetic evaluation. Misdiagnosis of individuals with HX as having HS is especially problematic since splenectomy is contraindicated in HX due to a greatly increased incidence of thromboembolic complications. Another diagnostic consideration concerns the use of osmotic fragility tests. Although osmotic fragility tests are frequently used to diagnose HX, ektacytometry provides greater accuracy. In the present study two patients who had ektacytometry results characteristic of HX had reportedly normal osmotic fragility tests in previous work-up. All individuals in our cohort with confirmed disease-causing mutations in PIEZO1 demonstrated the classic left shifted ektacytometry osmoscan indicative of erythrocyte dehydration. In addition, all individuals with these mutations demonstrated the expected decrease in erythrocyte potassium content not associated with a proportional increase in sodium. This illustrates the importance of specialized testing (ektacytometry and/or intracellular cation determinations) and the use of appropriately designed genetic panels to establish an accurate diagnosis in patients with hemolytic anemia of ambiguous phenotype, especially when splenectomy is being contemplated. DisclosuresQuinn:Amgen: Research Funding; Global Blood Therapeutics: Research Funding; Silver Lake Research Corporation: Research Funding.

Modified cantilever arrays improve sensitivity and reproducibility of nanomechanical sensing in living cells

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating network to propagate mechanical forces over both short and long length-scales. The findings provide mechanistic insights into how cancer cells interact with one another and with their microenvironments, enabling them to invade the surrounding tissues. Further, with this system it is possible to understand how cancer clusters are able to co-ordinate their migration through narrow blood capillaries.

Predicting the vascular adhesion of deformable drug carriers in narrow capillaries traversed by blood cells

In vascular targeted therapies, blood-borne carriers should realize sustained drug release from the luminal side towards the diseased tissue. In this context, such carriers are required to firmly adhere to the vessel walls for a sufficient period of time while resisting force perturbations induced by the blood flow and circulating cells. Here, a hybrid computational model, combining a Lattice Boltzmann (LBM) and Immersed Boundary Methods (IBM), is proposed for predicting the strength of adhesion of particles in narrow capillaries (7.5μm) traversed by blood cells. While flowing down the capillary, globular and biconcave deformable cells (7μm) encounter 2μm discoidal particles, adhering to the vessel walls. Particles present aspect ratios ranging from 0.25 to 1.0 and a mechanical stiffness varying from rigid (Ca = 0) to soft (Ca = 10−3). Cell–particle interactions are quantitatively predicted over time via three independent parameters: the cell membrane stretching δp; the cell-to-particle distance r, and the number of engaged ligand–receptor bonds NL. Under physiological flow conditions (Re = 10−2), rigid particles are detached and displaced away from the wall by blood cells. This is associated with a significant cell membrane stretching (up to 10%) and rapid breaking of molecular bonds (t umax/H <1). Differently, soft particles deform their shape as cells pass by, thus reducing force perturbations and extending the life of molecular bonds. Yet, only the thinnest deformable particles (2 ×0.5μm) firmly adhere to the walls under all tested configurations. These results suggest that low aspect ratio deformable particles can establish long-lived adhesive interactions with capillary walls, enabling de facto vascular targeted therapies.

Pendant drops shed from a liquid lens formed by liquid draining down the inner wall of a wide vertical tube

When a viscous liquid empties from an initially full, wide vertical tube, the drainage behaviour changes from a filament to a regime in which individual drops are shed by a lens formed at the end of the tube: liquid drains down the wall and the lens grows until it becomes unstable. This drop shedding regime was investigated for four Newtonian liquids (rapeseed oil, glycerol, honey and golden syrup) in three tube sizes and two tube materials (Bond number based on tube i.d. >1 in all cases). The drop mass increased modestly with flow rate and the equivalent sphere diameter, d, was strongly related to the capillary length Lc ≡ (γ/ρg)1/2 rather than the tube diameter. The results were fitted to a correlation of the form d/Lc = f(Bond, Reynolds, Morton, sine of the contact angle) derived from dimensional analysis. The data were compared with existing models for drop formation from filled narrow capillaries and a new, simple model based on a quasi-static model of the lens. Agreement with these models was poor, particularly for larger tubes, indicating the need for more detailed analysis. Insights into the dynamics, generated by video analysis of the lens shape, are presented.

Mathematical modelling of pressure-driven micropolar biological flow due to metachronal wave propulsion of beating cilia

In this paper, we present an analytical study of pressure-driven flow of micropolar non-Newtonian physiological fluids through a channel comprising two parallel oscillating walls. The cilia are arranged at equal intervals and protrude normally from both walls of the infinitely long channel. A metachronal wave is generated due to natural beating of cilia and the direction of wave propagation is parallel to the direction of fluid flow. Appropriate expressions are presented for deformation via longitudinal and transverse velocity components induced by the ciliary beating phenomenon with cilia assumed to follow elliptic trajectories. The conservation equations for mass, longitudinal and transverse (linear) momentum and angular momentum are reduced in accordance with the long wavelength and creeping Stokesian flow approximations and then normalized with appropriate transformations. The resulting non-linear moving boundary value problem is solved analytically for constant micro-inertia density, subject to physically realistic boundary conditions. Closed-form expressions are derived for axial velocity, angular velocity, volumetric flow rate and pressure rise. The transport phenomena are shown to be dictated by several non-Newtonian parameters, including micropolar material parameter and Eringen coupling parameter, and also several geometric parameters, viz eccentricity parameter, wave number and cilia length. The influence of these parameters on streamline profiles (with a view to addressing trapping features via bolus formation and evolution), pressure gradient and other characteristics are evaluated graphically. Both axial and angular velocities are observed to be substantially modified with both micropolar rheological parameters and furthermore are significantly altered with increasing volumetric flow rate. Free pumping is also examined. An inverse relationship between pressure rise and flow rate is computed which is similar to that observed in Newtonian fluids. The study is relevant to hemodynamics in narrow capillaries and also bio-inspired micro-fluidic devices.

Alignment and counting of mitochondria based on capillary electrophoresis

The mitochondria are referred to as the ‘power houses’ of the cell. The number of mitochondria is considered to be related to various diseases (e.g., obesity, degenerative diseases, and aging), and thus counting the number of mitochondria in per cell is helpful for the elucidation of the rare cells. Here, we report a mitochondria-aligning system that can realize mitochondrion counting based on capillary electrophoresis technology. By electrophoresis of fluorescent microsphere in a capillary with internal diameter approximated to the size of mitochondrion (0.5–1.5 μm), we find that the microsphere aggregated under DC voltage mode, corresponding to the peak intensity appeared much larger than that of one microsphere. After applying square-wave pulsed electric field, the fluorescence signal from one microsphere immediately appeared, indicating that the microsphere aligned one-dimensionally and migrated through a narrow capillary. Based on the above phenomenon, we evaluated the mitochondria in per cell of COS-1, NIH3T3, brown fat precursor cell, and brown fat cell, respectively.

Fast blood plasma separation device for point-of-care applications

In this work, a simple device for extremely fast separation of blood plasma from diluted whole blood was developed. The device accommodates an asymmetric polysulfone membrane/supporting membrane sandwich that allows collection of 10 µL blood plasma into a narrow glass capillary in less than 10 s. The composition of diluent solution was optimized in order to achieve maximum recoveries for selected metabolites of alcohol intoxication. 5% solution of [tris(hydroxymethyl)methylamino] propanesulfonic acid provided recoveries of formate, oxalate and glycolate close to 100% and only moderate erythrocyte lysis. Both charged and uncharged compounds from the whole blood samples can be analyzed in the separated blood plasma by capillary electrophoresis with contactless conductometric detection and spectrophotometry, respectively. The developed device might find wide application in on-site testing and point-of-care analysis, when only microliter volumes of whole blood are available.

Thermophoretically driven capillary transport of nanofluid in a microchannel

We investigate the interplay of thermophoretic force and interfacial tension on the capillary filling dynamics of a Newtonian nanofluid in a microchannel. In our model, we also consider an intricate thermofluidic coupling by taking the temperature dependence of viscosity aptly into account. This, in turn, determines the evolution of the viscous resistive force as the capillary front progresses, and presents an involved inter-connection between the driving thermophoretic force and the viscous resistive force. The two distinct regimes of particle transport in a fluid medium, delineated by particle size, are expounded to peruse the impact of imposed thermal gradients and particle size on particle retaining propensity of the nanofluid. Additionally, we witness a significant reduction in particle bearing proclivity of the nanofluid with enhancement in a thermal gradient. The results demonstrate the efficacy of the thermophoretic actuation towards the filling of narrow capillaries under the influence of a thermal gradient.

Inactivation of microorganisms by radical droplets from combination of water discharge and electro-spraying

We report the generation of radical droplets activated by an underwater electrical discharge and the sterilization of bacteria cells by spraying the radical droplets to open air. The plasma formed by electrical discharge in a narrow dielectric capillary tube produces atomic oxygen, atomic hydrogen, and hydroxyl radicals from the dissociation of water vapor, which is achieved through Joule heating in the narrow capillary tube. The capillary discharge electrode is placed in a water flow line, and the plasma-activated water is sprayed as fine droplets through a nozzle at 0.08 L/min. In a bactericidal test, the droplets show a sterilization effect of more than 99.99% after an exposure time of 3 h. The proposed radical droplet generator may also be useful for the elimination of airborne microorganisms.

Use of aTurn Coil and Channel Above a GMR-SV Device to Observe and Measure the Properties of Deoxidized Red Blood Cells Coupled to Magnetic Beads.

A giant magnetoresistance-spin valve (GMR-SV) having highly sensitive magnetic properties was prepared with a multilayer soft ferromagnetic/non-magnetic/pinned ferromagnetic/anti-ferromagnetic iridium manganese (IrMn) top layer (NiFe/CoFe/Cu/CoFe/IrMn) structure. Micron-sized magnetic beads (MBs) with a diameter of 1μm immersed in a solution containing 50 mg of Co-Si-OH/ml were attached to red blood cells (RBCs) having the very low magnetization of hemoglobin (HEM) to detect a deoxidized RBC combined with MBs (RBC+MBs). The RBC+MB combinations can be captured on a single-turn μ-coil that maintains a magnetic field large enough to detect the MBs attached to the RBC. When the RBC+MBs passes through a PR μ-channel with a width of 10μm, its stopping and starting are controlled by the electrical AC input signal applied to the single-turn μ-coil. The RBC+MBs combinations captured above the μ-device of the GMR-SV change the output signal and thus, can be used for detection. This observation implies that this device can be used as a biosensor to analyze the coupling force between the HEM and the MBs for RBCs with deformed membranes passing through a narrow capillary.

Investigation of red blood cell mechanical properties using AFM indentation and coarse-grained particle method

BackgroundRed blood cells (RBCs) deform significantly and repeatedly when passing through narrow capillaries and delivering dioxygen throughout the body. Deformability of RBCs is a key characteristic, largely governed by the mechanical properties of the cell membrane. This study investigated RBC mechanical properties using atomic force microscopy (AFM) with the aim to develop a coarse-grained particle method model to study for the first time RBC indentation in both 2D and 3D. This new model has the potential to be applied to further investigate the local deformability of RBCs, with accurate control over adhesion, probe geometry and position of applied force.ResultsThe model considers the linear stretch capacity of the cytoskeleton, bending resistance and areal incompressibility of the bilayer, and volumetric incompressibility of the internal fluid. The model’s performance was validated against force–deformation experiments performed on RBCs under spherical AFM indentation. The model was then used to investigate the mechanisms which absorbed energy through the indentation stroke, and the impact of varying stiffness coefficients on the measured deformability. This study found the membrane’s bending stiffness was most influential in controlling RBC physical behaviour for indentations of up to 200 nm.ConclusionsAs the bilayer provides bending resistance, this infers that structural changes within the bilayer are responsible for the deformability changes experienced by deteriorating RBCs. The numerical model presented here established a foundation for future investigations into changes within the membrane that cause differences in stiffness between healthy and deteriorating RBCs, which have already been measured experimentally with AFM.

Transient penetration of a viscoelastic fluid in a narrow capillary channel

This article describes an unexplored transport phenomenon where a mildly viscoelastic medium encroaches a narrow capillary channel under the action of surface-tension force. The ultimate goal of the study is to provide the penetration length and the intrusion rate of the liquid as functions of time. The resulting analysis would be instrumental in building an inexpensive and convenient rheometric device which can measure the temporal scale for viscoelastic relaxation from the stored data of the aforementioned quantities. The key step in the formulation is a transient eigenfunction expansion of the instantaneous velocity profile. The time-dependent amplitude of the expansion as well as the intruded length are governed by a system of integro-differential relations which are derived by exploiting the mass and momentum conservation principles. The obtained integro-differential equations are simultaneously solved by using a fourth-order Runge–Kutta method assuming a start-up problem from rest. The resulting numerical solution properly represents the predominantly one-dimensional flow which gradually slows down after an initial acceleration and subsequent oscillation. The computational findings are independently verified by two separate perturbation theories. The first of these is based on a Weissenberg number expansion revealing the departure in the unsteady imbibition due to small but finite viscoelasticity. In contrast, the second one explains the long-time behaviour of the system by analytically predicting the decay features of the dynamics. These asymptotic results unequivocally corroborate the simulation inferring the accuracy of the numerics as well as the utility of the simplified mathematical models.

The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged Bronchiole to Study the Microbiology of Lung Infections.

Many chronic airway diseases result in mucus plugging of the airways. Lungs of an individual with cystic fibrosis are an exemplary case where their mucus-plugged bronchioles create a favorable habitat for microbial colonization. Various pathogens thrive in this environment interacting with each other and driving many of the symptoms associated with CF disease. Like any microbial community, the chemical conditions of their habitat have a significant impact on the community structure and dynamics. For example, different microorganisms thrive in differing levels of oxygen or other solute concentrations. This is also true in the CF lung, where oxygen concentrations are believed to drive community physiology and structure. The methods described here are designed to mimic the lung environment and grow pathogens in a manner more similar to that from which they cause disease. Manipulation of the chemical surroundings of these microbes is then used to study how the chemistry of lung infections governs its microbial ecology. The method, called the WinCF system, is based on artificial sputum medium and narrow capillary tubes meant to provide an oxygen gradient similar to that which exists in mucus-plugged bronchioles. Manipulating chemical conditions, such as the media pH of the sputum or antibiotics pressure, allows for visualization of the microbiological differences in those samples using colored indicators, watching for gas or biofilm production, or extracting and sequencing the nucleic acid contents of each sample.