Shape Of Red Blood Cells Research Articles

Axial and Nonaxial Migration of Red Blood Cells in a Microtube.

Human red blood cells (RBCs) are subjected to high viscous shear stress, especially during microcirculation, resulting in stable deformed shapes such as parachute or slipper shape. Those unique deformed RBC shapes, accompanied with axial or nonaxial migration, cannot be fully described according to traditional knowledge about lateral movement of deformable spherical particles. Although several experimental and numerical studies have investigated RBC behavior in microchannels with similar diameters as RBCs, the detailed mechanical characteristics of RBC lateral movement—in particular, regarding the relationship between stable deformed shapes, equilibrium radial RBC position, and membrane load—has not yet been fully described. Thus, we numerically investigated the behavior of single RBCs with radii of 4 m in a circular microchannel with diameters of 15 m. Flow was assumed to be almost inertialess. The problem was characterized by the capillary number, which is the ratio between fluid viscous force and membrane elastic force. The power (or energy dissipation) associated with membrane deformations was introduced to quantify the state of membrane loads. Simulations were performed with different capillary numbers, viscosity ratios of the internal to external fluids of RBCs, and initial RBC centroid positions. Our numerical results demonstrated that axial or nonaxial migration of RBC depended on the stable deformed RBC shapes, and the equilibrium radial position of the RBC centroid correlated well with energy expenditure associated with membrane deformations.

Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives

A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe3+-Fe2+ reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical. Moreover, the indolyl radical stabilization and the presence of unsubstituted indole nitrogen atom are mandatory for the observed antioxidant activity, which strongly depends on the type of the substituent directly connected to the methylene group at the C-3 position. Human red blood cells (RBC) have been used as a cell model to study derivatives interaction with the cell membrane. Haemolytic activity and RBC shape transformation were observed for certain derivatives in a concentration-dependent manner. However, most of the derivatives at sublytic concentration showed high cytoprotective activity against oxidative haemolysis induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The cytoprotective properties of derivatives can be explained mostly due to their interactions with the RBC membrane components. Taking together, theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds.

Hydration of methemoglobin studied by in silico modeling and dielectric spectroscopy.

The hemoglobin concentration of 35 g/dl of human red blood cells is close to the solubility threshold. Using microwave dielectric spectroscopy, we have assessed the amount of water associated with hydration shells of methemoglobin as a function of its concentration in the presence or absence of ions. We estimated water-hemoglobin interactions to interpret the obtained data. Within the concentration range of 5-10 g/dl of methemoglobin, ions play an important role in defining the free-to-bound water ratio competing with hemoglobin to recruit water molecules for the hydration shell. At higher concentrations, hemoglobin is a major contributor to the recruitment of water to its hydration shell. Furthermore, the amount of bound water does not change as the hemoglobin concentration is increased from 15 to 30 g/dl, remaining at the level of ∼20% of the total intracellular water pool. The theoretical evaluation of the ratio of free and bound water for the hemoglobin concentration in the absence of ions corresponds with the experimental results and shows that the methemoglobin molecule binds about 1400 water molecules. These observations suggest that within the concentration range close to the physiological one, hemoglobin molecules are so close to each other that their hydration shells interact. In this case, the orientation of the hemoglobin molecules is most likely not stochastic, but rather supports partial neutralization of positive and negative charges at the protein surface. Furthermore, deformation of the red blood cell shape results in the rearrangement of these structures.

Surface model of the human red blood cell simulating changes in membrane curvature under strain

We present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.

Microfluidic Obstacle Arrays Induce Large Reversible Shape Change in Red Blood Cells.

Red blood cell (RBC) shape change under static and dynamic shear stress has been a source of interest for at least 50 years. High-speed time-lapse microscopy was used to observe the rate of deformation and relaxation when RBCs are subjected to periodic shear stress and deformation forces as they pass through an obstacle. We show that red blood cells are reversibly deformed and take on characteristic shapes not previously seen in physiological buffers when the maximum shear stress was between 2.2 and 25 Pa (strain rate 2200 to 25,000 s−1). We quantify the rates of RBC deformation and recovery using Kaplan–Meier survival analysis. The time to deformation decreased from 320 to 23 milliseconds with increasing flow rates, but the distance traveled before deformation changed little. Shape recovery, a measure of degree of deformation, takes tens of milliseconds at the lowest flow rates and reached saturation at 2.4 s at a shear stress of 11.2 Pa indicating a maximum degree of deformation was reached. The rates and types of deformation have relevance in red blood cell disorders and in blood cell behavior in microfluidic devices.

Combining microfluidics with machine learning algorithms for RBC classification in rare hereditary hemolytic anemia

Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic device mimicking the slits of the spleen red pulp area and video data analysis are combined for the characterization of RBCs in RHHA. This microfluidic unit is designed to evaluate RBC deformability by maintaining them fixed in planar orientation, allowing the visual inspection of RBC’s capacity to restore their original shape after crossing microconstrictions. Then, two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%.

Clot Formation Under Physiological Flow Conditions Is Altered in Sickle Cell Disease As Measured By a Multiparameter Microfluidic System

Background: While the hallmark of sickle cell disease (SCD) is vaso-occlusion, it is now clear that hypercoagulation plays a prominent role in the pathophysiology of SCD (Sparkenbaugh 2017). Consistent with this prothrombotic state, SCD patients remain at increased risk for thromboembolic events (Naik 2014) such as pulmonary embolism and deep vein thrombosis. In addition, sickle red blood cells (RBC) are known to biochemically contribute to the hypercoaguable state through hemolysis or enhanced PS exposure (Whelihan 2016, Litvinov 2017). However, no studies have examined the biophysical contribution of RBCs to clot formation in SCD, especially under physiologic flow conditions. As both the increased stiffness and adhesion of the sickle RBC (Kasschau 2016) biophysically amplify the frequency and duration of interactions with the developing clot, we hypothesize that enhanced RBC incorporation occurs in sickle cell clots under physiologic flow conditions. Furthermore, as the altered shape and stiffness of sickle RBCs decreases the packing density in clots (Tutwiler 2015, Strauss 2015), we also hypothesize that the application of fluidic forces to the clots likely causes instability potentially leading to thromboemboli. This highlights the need for an assay that studies both clot formation and stability under flow conditions.Innovation: While studying these events in vivo remains the most physiologically relevant approach, the inability to control the cellular and physical parameters renders mechanistic studies to be extremely challenging. Moreover, while in vitro microfluidics offer the unique ability to precisely control parameters known to affect clot formation, including shear stress, hematocrit, platelet count, and oxygen tension, these devices typically cannot be used for extended time studies due to confounding systemic clotting throughout the fluidic. To that end, we developed a novel multi-parameter microfluidic that precisely controls the spatial location of clot initiation and formation for extended (>30 mins) in vitro studies of developing clots using recalcified citrated whole blood (Figure 1a). Our easy-to-use system combines on-chip calcification (Lehmann 2015) to reduce systemic clotting, simple assembly methods (Myers 2017), and protein micropatterning using collagen and tissue factor. Brightfield and fluorescent microscopy was used to examine the flow of blood over this patch to observe the clot formation process, structure, and stability.Results: The device performed as designed and maintained perfusion for at least 45 minutes with each trial for healthy AA donors (Figure 1b). Our preliminary images qualitatively show that clots from SS patients on hydroxyurea are larger than AA clots (Figure 1b-c). Quantitative measurements of the clot areas indicate that the clot size is significantly higher in SCD blood (n=3 patients, Mann-Whitney, p= 0.007) than in blood from healthy AA subjects (n=21) (Figure 1d). This suggests that even in the modern age of hydroxyurea therapy, patients remain in a prothrombotic state. Furthermore, after SCD whole blood clots were formed in our microfluidic system, force applied via continuous exposure to high shear stress of ~3000 dynes/cm2 in the microfluidic created clot fragments composed primarily of RBCs. The creation of these fragments suggests decreased clot stability and has implications for micro-thromboemboli (Figure 1e). These results support our hypothesis that enhanced RBC incorporation in SCD alters the structure and stability of whole blood clots. Ongoing studies are focused on defining the compositional variability and susceptibility to embolism.Conclusion and Relevance: Ongoing studies involve integrating and varying shear stress, hematocrit, platelet count, and oxygen tension to determine how these multiple parameters interact to affect the incorporation of sickle RBCs in thrombi, as our novel microfluidic enables real time visualization of clot formation and clot stability under physiologic flow conditions (Figure 2). Our device allows us to examine the stability of these clots under shear stress and the propensity for emboli formation. Collectively, these studies will lead to a better understanding of the prothrombotic state of SCD and how the sickle RBCs interacts with platelets and the coagulation cascade. [Display omitted] DisclosuresLam:Sanguina, LLC: Equity Ownership.

AN EFFICIENT IDENTIFICATION OF RED BLOOD CELL EQUILIBRIUM SHAPE USING NEURAL NETWORKS

This work of applied mathematics with interfaces in bio-physics focuses on the shape identification and numerical modelisation of a single red blood cell shape. The purpose of this work is to provide a quantitative method for interpreting experimental observations of the red blood cell shape under microscopy. In this paper we give a new formulation based on classical theory of geometric shape minimization which assumes that the curvature energy with additional constraints controls the shape of the red blood cell. To minimize this energy under volume and area constraints, we propose a new hybrid algorithm which combines Particle Swarm Optimization (PSO), Gravitational Search (GSA) and Neural Network Algorithm (NNA). The results obtained using this new algorithm agree well with the experimental results given by Evans et al. (8) especially for sphered and biconcave shapes.

Effects of mobile phone emissions on human red blood cells.

Raman spectroscopy was performed on GSM 900 and 1800 MHz mobile phone signal exposed red blood cells (RBCs). The observed changes in the Raman spectra of mobile signal exposed RBCs compared to unexposed control suggest reduced hemoglobin-oxygen affinity for the exposed cells. The possible mechanism may involve activation of the voltage gated membrane Ca2+ channels by the mobile phone emissions resulting in an increase in the levels of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) in cells via altered metabolic activities. Further studies carried out with fluorescent Ca2+ indicator confirmed increased intracellular Ca2+ level in the exposed cells. Since intracellular ATP level influences the shape and mechanics of RBCs, exposed cells were studied using diffraction phase microscopy and optical tweezers. Detectable changes in shape and mechanical properties were observed due to mobile signal exposure.

Changes in Leukogram and Erythrogram Results in Bitches with Vaginitis.

Simple SummaryInflammatory diseases of the reproductive tract of bitches are a common problem in veterinary practice. Vaginitis, which is an inflammation of the vagina, may have various causes and degrees of severity. The aim of this study was to analyze whether the inflammation of the vagina in dogs causes changes in the parameters of white blood cells (leukogram, which is the percentage of individual types of white blood cells) and red blood cells (erythrogram, changes in the shape of erythrocytes). The obtained results suggest that leukogram and erythrogram analyses may be useful diagnostic tools in veterinary practice.Vaginitis in female dogs is a problem most veterinarians face in their practice. It manifests as localized inflammation, and its variable etiology and different severities often make diagnosis problematic. The study consisted of comparing blood smears taken from 16 animals: 8 healthy bitches and 8 bitches with confirmed vaginitis. We analyzed the percentage of different types of white blood cells (leukogram) and changes in the shape of red blood cells (erythrogram) in both groups. We observed changes in red blood cell morphology, i.e., a higher percentage of lacrimocytes and schistocytes in female dogs with vaginitis compared to their healthy counterparts. The observed hematological changes may illustrate the severity of inflammation. The analysis of erythrograms showed a significantly higher percentage of lacrimocytes and schistocytes in diseased bitches (1.58 ± 1.19% and 0.13 ± 0.12%) compared to healthy animals (0.58 ± 0.38 and 0.00 ± 0.00, respectively). The obtained results may indicate that the analysis of erythrograms throughout the course of vaginitis in bitches may constitute a diagnostic tool, as opposed to the analysis of leukograms, which is more sensitive when it comes to the systemic inflammatory response of the organism. It seems that simultaneous analysis of erythrograms and leukograms may facilitate the diagnostic process in clinical practice.

The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib.

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.

Importance of Viscosity Contrast for the Motion of Erythrocytes in Microcapillaries

The dynamics and deformation of red blood cells (RBCs) in microcirculation affect the flow resistance and transport properties of whole blood. One of the key properties that can alter RBC dynamics in flow is the contrast λ (or ratio) of viscosities between RBC cytosol and blood plasma. Here, we study the dependence of RBC shape and dynamics on the viscosity contrast in tube flow, using mesoscopic hydrodynamics simulations. State diagrams of different RBC dynamical states, including tumbling cells, parachutes, and tank-treading slippers, are constructed for various viscosity contrasts and wide ranges of flow rates and tube diameters (or RBC confinements). Despite similarities in the classification of RBC behavior for different viscosity contrasts, there are notable differences in the corresponding state diagrams. In particular, the region of parachutes is significantly larger for λ = 1 in comparison to λ = 5. Furthermore, the viscosity contrast strongly affects the tumbling-to-slipper transition, thus modifying the regions of occurrence of these states as a function of flow rate and RBC confinement. Also, an increase in cytosol viscosity leads to a reduction in membrane tension induced by flow stresses. Physical mechanisms that determine these differences in RBC dynamical states as a function of λ are discussed.

Red Blood Cell (RBC) Echinocyte SEM Structure Directly Affected by Oxygen, Heat and F‐actin Destabilization

The RBC cytoskeleton is a spectrin-actin meshwork tethered to the integral membrane protein, band 3, through several proteins, including ankyrin. Their interactions affect membrane curvature, mechanics, microdomain formation, and may participate in oxygenation of hemoglobin (Hb) as deoxyHb displaces ankyrin to bind band 3. Our focus is to understand how hypoxia and elevated temperature cause RBC shape changes that may impact microvascular rouleaux formation and vessel blockage with thermal burn injury. We hypothesized that both oxygen and F-actin destabilization are required for shape change. Washed human RBCs (BioIVT) suspended in saline with 1% DMSO, 3.7μM Jasplakinolide (JASPA, polymerizes F-actin), 26.14μM Latrunculin A (LatA, depolymerizes F-actin), 0.5μM Cytochalasin D (CytoD, disrupts cytoskeleton), 2μM 4,4ʹ-diisothiocyano-2,2ʹ-stilbenedisulfonic acid (DIDS, binds band 3, untethers cytoskeleton from membrane) or control (platelet poor plasma, PPP). Each was tested at 2 temperatures (T: 37, 45°C) and 3 oxygen levels (O2: 0, 5, 10%). At T/O2, suspensions were fixed with 1.5% paraformaldehyde 1.5% glutaraldehyde, then with OsO4. Samples were serially dehydrated in ethanol, and coated with 12-15nm Au-Pd in Ar (6mA, Polaron E5100). SEM images (FEI Nova NanoSEM 450, high vacuum mode 4-5 mm working distance, beam 2kV, Everhart-Thornley Detector) were obtained and analyzed using ImageJ (NIH) for 44 samples and 656 RBC. RBC long and short diameters were obtained. For echinocytes (ECH), ‘edge’ spicule (seen on periphery), height, H, width at base (BW) and mid-height (MW) were measured; ‘face’ spicule (seen on presenting face) topology was measured (inter-node distances, nearest neighbors, angles). RBC were classified per the clinical standard as biconcave (discocyte), ECH-I (short broad spicules, flat cell), ECH-II (formed spicules, elliptical cell), ECH-III (well formed spicules, spherical). Independent of treatment, T or O2, we first confirmed that spicule shape progressed to taller with a narrower base, with closer packed conformation as ECH progressed from I to III. Independent of treatment or O2, spicules at 45°C for ECH-I were smaller in H and BW/MW, and more closely packed than at 37°C; ECH-II/III only displayed closer packing. In PPP ECH-I spicules at 0%/37°C were broader and further spaced, while spicules at 10%/45°C were significantly smaller in BW/MW and closer packed; ECH-II/III were not affected by oxygen. Concentrating on ECH-I, DIDS removed the effects on W and spacing at all oxygen/temps. Actin destabilization (CytoD) removed the effect of O2 and T on W, but not spacing; while depolymerization (LatA) had little effect on W or spacing. Actin polymerization (JASPA) had no effect on W, but removed the effect of O2 on spacing. Thus, decoupling the cytoskeleton from band 3 (0% oxygen or DIDS) resulted in fewer broad spicules; depolymerization only (LatA) had little effect, while destabilization (CytoD) reduced the W but not spacing of spicules, and polymerization (JASPA) affected spacing but not W.

AQP1 and RhAG proteins play roles on oxygen offloading from murine red blood cells during aging

The diffusion of O2 across the red blood cell (RBC) membrane is critical for life. Although the traditional view had been that all O2 moves through RBC membranes by dissolving in and diffusing through the membrane lipid, our recent work (bioRxiv. doi:10.1101/2020.08.28.265066) indicates that this is not the case. Using stopped-flow absorbance spectroscopy to monitor the hemoglobin (Hb) absorbance spectrum in intact RBCs, we found that, compared with RBCs from wild-type (WT) mice, those from double knockout (dKO) mice genetically deficient in both aquaporin-1 (AQP1) and the rhesus (Rh) protein exhibit a 1/3 decrease in the rate constant for O2 offloading from Hb (kHbO2). Mathematical simulations show that this 1/3 decrease in kHbO2 corresponds to a ~55% decrease in the membrane permeability to O2 (PM,O2). In previous abstracts, we reported that the kHbO2 of RBCs from WT mice are indistinguishable from age 2–3 months through 12 months, but begins to fall at 18 months, and drops by ~13% at 29 months—the lifespan of our mice. However, the relatively low kHbO2 of RBCs from dKO mice remains stable through 29 months. In addition to increasing the number of observations for aging WT and dKO mice, we now report the effect of aging on the kHbO2 of RBCs from mice genetically deficient in just RhAG, studying mice at six ages (2–3 months, 6 months, 12 months, 18 months, 24 months, and 29 months). The kHbO2 of RBCs from RhAG-KO mice begins ~17% lower than that of WT mice at 2–3 months (see above bioRxiv ref.), and remains stable through 29 months (N = 5 to 8 at 6–24 months, 4 at 29 months), similar to that of dKO mice. Changes in hematological parameters or RBC size and shape cannot explain the observed decreases in kHbO2 in WT mice. RBC proteomics data on a single WT mouse at 29 months suggests decreases in AQP1 (11%), RhAG (19%), and mRh (27%), and AE1 (22%). We conclude from our dKO and RhAG-KO data that the non-AQP1/RhAG component of RBC membrane O2 permeability is independent of aging, and that the age-related fall in kHbO2 in WT mice is likely to be due, at least in part, to age-related decreased functional expression (i.e., combination of protein number and activity of individual proteins) of AQP1 and RhAG —which function asO2 channels. We continue to build our number of observations on WT, dKO, and RhAG-KO mice of various ages, and are now extending our work to RBCs from mice genetically deficient in just AQP1.

DOMINANCE OF HERBAL MEDICINES IN TREATING SICKEL CELL ANEMIA

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical problems. Several drugs are available for treating SCD, these medicines are insufficiently effective, toxic, or too expensive to be used. So there is a need to arise a safe, effective, and inexpensive therapeutic agent from indigenous plants used in ethnomedicines. SCD is affecting millions of people worldwide. Due to lack of progress in drug discovery and appropriate treatment methods, victims often turn to traditional Ayurvedic medicines that take advantage of the plant extracts. The use of complementary and alternative medicine (CAM) has been thought worldwide, most especially in patients with chronic diseases. SCD is one of such chronic diseases. Sickle cell anemia (SCA) has been treated for ages with natural products, especially herbs and Ayurvedic medicines worldwide. The proven medicines for sickle cell anemia includes, the use of hydroxyurea, folic acid and amino acids supplementation that manage the condition of blood transfusions and stabilize the patient’s hemoglobin level. But these clinical treatments are quite expensive and have attendant risk factors. As a research for medicinal plants into anti-sickling properties has been satisfy, so the alternative therapy of using phytomedicines has proven to reduce the crisis and reverse for sickling of RBC’s. As the use of medicinal plants and nutrition in managing SCD is gaining attention so the enormous benefits of phyto-medicine and nutraceuticals are discussed in this paper. Here in we have summarized the use of tradition Ayurvedic medicines in treating SCA.

β-Carotene-Induced Alterations in Haemoglobin Affinity to O2.

β-Carotene (β-Crt) can be dispersed in hydrophobic regions of the membrane of red blood cells (RBC). Its location, orientation and distribution strongly depend on carotenoid concentration. In the present pilot trial (six human subjects involved), it is demonstrated that incubation of RBCs with β-Crt (1.8 × 107 β-Crt molecules per RBC, 50 μmol/L) results in expansion of the membrane of RBCs and slight elongation of the cell. The changes are of statistical significance, as verified by the Wilcoxon test at p < 0.05. They indicate (i) a highly random orientation and location of β-Crt inside the membrane and (ii) a tendency for its interaction with membrane skeleton proteins. The accompanying effect of decreased RBC resistance to lysis is possibly a result of the incorrect functioning of ion channels due to their modification/disruption. At higher β-Crt concentrations, its clustering inside membranes may occur, leading to further alterations in the shape and size of RBCs, with the most pronounced changes observed at 1.8 × 108 β-Crt molecules per RBC (500 μmol/L). Due to the reduced permeability of ions, such membranes exhibit increased resistance to haemolysis. Finally, we show that interactions of β-Crt with the membrane of RBCs lead to an alteration in haemoglobin-oxygen affinity, shifting the oxyhaemoglobin dissociation curve toward higher oxygen partial pressures. If the impact of β-Crt on a curve course is confirmed in vivo, one may consider its role in the fine tuning of O2 transportation to tissues. Hence, at low concentrations, providing unchanged elastic and functional properties of RBCs, it could serve as a beneficial agent in optimising heart performance and cardiovascular load.

A Molecular Communication Detection Method for the Deformability of Erythrocyte Membrane in Blood Vessels.

Molecular communication (MC) inspired drug delivery holds considerable promise as a new design for targeted therapy with high efficiency and minimal toxicity. The process of drug delivery can be modelled in a blood flow-based MC system, where nanoparticles (NPs) carry therapeutic agents through the blood vessel channels to the targeted diseased tissue. Most previous studies in the flow-based MC consider a Newtonian fluid with a laminar flow, which ignores the influence of red blood cells (RBCs). However, the nature of blood flow is a complex and non-Newtonian fluid composed of proteins, platelets, plasma and deformable cells, especially RBCs. The ability to change their shapes is essential to the proper functioning of RBCs in the microvasculature. Different shapes of RBCs have a great impact on the performance of blood flow. Changes in the properties and shapes of RBCs are often associated with different diseases, such as sickle cell anemia, diabetes, and malaria. Thus, it is highly important to establish a more realistic blood flow MC model considering the deformable cells. According to our previous study, the motion and adhesion of individual NPs are modelled through the Brownian adhesion dynamics. Subsequently, this paper establishes a particle-cell hybrid model in the flow-based MC, which focuses on the RBC deformation, aggregation, and dispersion in the blood suspension. Based on the state of the RBC deformation and aggregation in the vessels with different flow rates, this paper proposes a novel methodology for detecting the deformability of the cells. The blood state in terms of RBC deformability is determined by the difference in NPs' concentration at the receiving end., this paper sheds some light on the influence of RBCs on the motion of NPs, which provides new insights on the design of targeted drug delivery and the detection of vascular diseases.

On the Role of Curved Membrane Nanodomains, and Passive and Active Skeleton Forces in the Determination of Cell Shape and Membrane Budding.

Biological membranes are composed of isotropic and anisotropic curved nanodomains. Anisotropic membrane components, such as Bin/Amphiphysin/Rvs (BAR) superfamily protein domains, could trigger/facilitate the growth of membrane tubular protrusions, while isotropic curved nanodomains may induce undulated (necklace-like) membrane protrusions. We review the role of isotropic and anisotropic membrane nanodomains in stability of tubular and undulated membrane structures generated or stabilized by cyto- or membrane-skeleton. We also describe the theory of spontaneous self-assembly of isotropic curved membrane nanodomains and derive the critical concentration above which the spontaneous necklace-like membrane protrusion growth is favorable. We show that the actin cytoskeleton growth inside the vesicle or cell can change its equilibrium shape, induce higher degree of segregation of membrane nanodomains or even alter the average orientation angle of anisotropic nanodomains such as BAR domains. These effects may indicate whether the actin cytoskeleton role is only to stabilize membrane protrusions or to generate them by stretching the vesicle membrane. Furthermore, we demonstrate that by taking into account the in-plane orientational ordering of anisotropic membrane nanodomains, direct interactions between them and the extrinsic (deviatoric) curvature elasticity, it is possible to explain the experimentally observed stability of oblate (discocyte) shapes of red blood cells in a broad interval of cell reduced volume. Finally, we present results of numerical calculations and Monte-Carlo simulations which indicate that the active forces of membrane skeleton and cytoskeleton applied to plasma membrane may considerably influence cell shape and membrane budding.

Impact of Liposomal Drug Formulations on the RBCs Shape, Transmembrane Potential, and Mechanical Properties.

Liposomal technologies are used in order to improve the effectiveness of current therapies or to reduce their negative side effects. However, the liposome–erythrocyte interaction during the intravenous administration of liposomal drug formulations may result in changes within the red blood cells (RBCs). In this study, it was shown that phosphatidylcholine-composed liposomal formulations of Photolon, used as a drug model, significantly influences the transmembrane potential, stiffness, as well as the shape of RBCs. These changes caused decreasing the number of stomatocytes and irregular shapes proportion within the cells exposed to liposomes. Thus, the reduction of anisocytosis was observed. Therefore, some nanodrugs in phosphatidylcholine liposomal formulation may have a beneficial effect on the survival time of erythrocytes.

Experimental evaluation of heat transfer performance under natural and forced convection around a phase change material encapsulated in various shapes

Cold thermal energy storage can reduce peak electricity use in electric air conditioning systems as well as improve free space cooling, through convective heat transfer between a surrounding fluid (heat transfer fluid or air) and encapsulated phase change material (PCM). In this work, heat transfer performances and phase change behaviours of six PCM capsules with equal-volumes but varying-shapes were studied experimentally, for use in cold latent heat storage. A tetra-n-butylammonium bromide-based PCM with an adjustable phase change temperature of 0–12 °C was injected into capsules of spherical, cylindrical (short and long), pyramidal, tetrahedral, and a biomimetic red blood cell shape. First, an infrared camera recorded the surface temperature variation during the melting process of each capsule in air under natural convection. Second, an experimental setup was built to investigate latent heat storage during the freezing and melting processes for each shape under forced convection, focusing on the effects of fluid temperature, flowrate and PCM capsule tilt angle on freezing and melting times. The results showed that the freezing and melting times were dependent on not only the surface area to volume ratio, but also on the distance from centroid to inner capsule surface. Importantly, the red blood cell shape was found to be the most favourable geometry because it yielded the most rapid freezing and melting process, which were further enhanced in a configuration where the freestream flow directly impinged onto its centroid. The work is a pioneering study on the effects of PCM capsule geometry, providing experimental data and recommendations for future studies on CTES and applications.