Elasticity Of Red Blood Cells Research Articles

Comparative Study of Computational Methods for Classifying Red Blood Cell Elasticity

Comparative Study of Computational Methods for Classifying Red Blood Cell Elasticity

Optical tweezers to measure the elasticity of red blood cells: a tool to study the erythrocyte response to antimalarials

The Plasmodium falciparum parasite infected more than 240 million people and killed around 600,000 patients last year alone. A key aspect of the pathophysiology of P. falciparum is the increased rigidity and adhesiveness of the membrane of infected red blood cells (iRBC). Optical tweezers (OT) have been proposed as a tool to evaluate and screen potential drugs because they can provide valuable information to determine a drug’s mechanism of action. The OT experimental design of this study was used to compare the plasma membrane stiffness of uninfected RBCs (uRBCs) and iRBCs, showing that the iRBCs were four times more rigid. The increased rigidity was more evident in those RBCs infected by the P. falciparum schizont stage. We also characterized the membrane deformability of iRBCs in vitro under the active concentration of common antimalarials on drug-resistant and non-drug-resistant P. falciparum strains. In addition, we also determined that the increased membrane rigidity of uRBCs during P. falciparum infection, known as the bystander effect, is partially reversed by antimalarial drugs. These findings suggest that single-cell mechanical measurements have potential uses in personalized medicine by characterizing the response to malaria treatment.

Classification of Red Blood Cells Using Time-Distributed Convolutional Neural Networks from Simulated Videos

The elasticity of red blood cells (RBCs) plays a vital role in their efficient movement through blood vessels, facilitating the transportation of oxygen within the bloodstream. However, various diseases significantly impact RBC elasticity, making it an important parameter for diagnosing and monitoring health conditions. In this study, we propose a novel approach to determine RBC elasticity by analyzing video recordings and using a convolutional neural network (CNN) for classification. Due to the scarcity of available blood flow recordings, computer simulations based on a numerical model are employed to generate a substantial amount of training data. The simulation model incorporates the representation of RBCs as elastic objects within a fluid flow, allowing for a detailed understanding of their behavior. We compare the performance of different CNN architectures, including ResNet and EfficientNet, for video classification of RBC elasticity. Our results demonstrate the potential of using CNNs and simulation-based data for the accurate classification of RBC elasticity.

Editorial: theme issue on complex rheology in biological systems

Editorial: theme issue on complex rheology in biological systems

Computational Study of Methods for Determining the Elasticity of Red Blood Cells Using Machine Learning

RBC (Red Blood Cell) membrane is a highly elastic structure, and proper modelling of this elasticity is essential for biomedical applications that involve computational experiments with blood flow. In this work, we present a new method for estimating one of the key parameters of red blood cell elasticity, which uses a neural network trained on the simulation outputs. We test classic LSTM (Long-Short Term Memory) architecture for the time series regression task, and we also experiment with novel CNN-LSTM (Convolutional Neural Network) architecture. We paid special attention to investigating the impact of the way the three-dimensional training data are reduced to their two-dimensional projections. Such a comparison is possible thanks to working with simulation outputs that are equivalently defined for all dimensions and their combinations. The obtained results can be used as recommendations for an appropriate way to record real experiments for which the reduced dimension of the acquired data is essential.

Prophylaxis of Reperfusion Complications in Treatment of Acute Myocardial Infarction in Type 2 Diabetes Mellitus Patients

Purpose — to identify the possibility of improving the outcome of multimodality treatment of acute myocardial infarction (AMI) in type 2 diabetes mellitus (DM) patients by use of a succinate-containing drug.Materials and methods. The results of examination and treatment of 86 men aged 40 to 70 years with clinical diagnosis of AMI and concomitant type 2 DM were analyzed. The patients were split into two groups depending on use of the succinate-containing drug. Patients of the control group (38 men, 58.3±7.1 years old) received the standard treatment that included percutaneous coronary intervention (PCI). In the main group under study (48 men, 57.6±7.6 years old), the standard therapy complex was complemented with administration of a succinate-containing drug (1.5% succinic acid solution), which was administered first 30–60 minutes prior to PCI intravenously at a dose of 10–12 ml/kg; then, daily once a day, for 5 days at a dose of 5–6 ml/kg. Peculiarities of the AMI clinical course, dynamics of myocardial contractility, values of acid-base balance (ABB), glucose and lactate content, lipid peroxidation (LPO) and antioxidant system (AOS), rheological properties of the blood were evaluated.Results. During AMI type 2 DM patients developed compensated metabolic lactic acidosis and oxidative distress that manifested in considerable activation of LPO and insufficient activity of the enzymatic component of AOS, blood viscosity grew, elasticity of red blood cells fell. Decreased local and global myocardial contractility was noted as well. During PCI in this category of patients, cardiac rhythm disorders developed in 47.4% of cases, 23.7% of which were life threatening, such as multifocal ventricular extra systole and ventricular fibrillation. Conclusion. Administration of a succinate-containing drug during performance of PCI provided correction of the lipid peroxidation processes and rheological properties of the blood in the population studied, facilitated improvement of left ventricle’s systolic and diastolic function, reduced the risk of reperfusion complications.

Image-based model of the spectrin cytoskeleton for red blood cell simulation.

We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.

Automatic real time evaluation of red blood cell elasticity by optical tweezers.

Optical tweezers have been used to trap, manipulate, and measure individual cell properties. In this work, we show that the association of a computer controlled optical tweezers system with image processing techniques allows rapid and reproducible evaluation of cell deformability. In particular, the deformability of red blood cells (RBCs) plays a key role in the transport of oxygen through the blood microcirculation. The automatic measurement processes consisted of three steps: acquisition, segmentation of images, and measurement of the elasticity of the cells. An optical tweezers system was setup on an upright microscope equipped with a CCD camera and a motorized XYZ stage, computer controlled by a Labview platform. On the optical tweezers setup, the deformation of the captured RBC was obtained by moving the motorized stage. The automatic real-time homemade system was evaluated by measuring RBCs elasticity from normal donors and patients with sickle cell anemia. Approximately 150 erythrocytes were examined, and the elasticity values obtained by using the developed system were compared to the values measured by two experts. With the automatic system, there was a significant time reduction (60×) of the erythrocytes elasticity evaluation. Automated system can help to expand the applications of optical tweezers in hematology and hemotherapy.

A Deep Intronic Mutation in the Ankyrin-1 Gene Causes Diminished Protein Expression Resulting in Hemolytic Anemia in Mice

Linkage between transmembrane proteins and the spectrin-based cytoskeleton is necessary for membrane elasticity of red blood cells. Mutations of the proteins that mediate this linkage result in various types of hemolytic anemia. Here we report a novel N-ethyl-N-nitrosourea−induced mutation of ankyrin-1, named hema6, which causes hereditary spherocytosis in mice through a mild reduction of protein expression. The causal mutation was traced to a single nucleotide transition located deep into intron 13 of gene Ank1. In vitro minigene splicing assay revealed two abnormally spliced transcripts containing cryptic exons from fragments of Ank1 intron 13. The inclusion of cryptic exons introduced a premature termination codon, which leads to nonsense-mediated decay of the mutant transcripts in vivo. Hence, in homozygous mice, only wild-type ankyrin-1 is expressed, albeit at 70% of the level in wild-type mice. Heterozygotes display a similar hereditary spherocytosis phenotype stemming from intermediate protein expression level, indicating the haploinsufficiency of the mutation. Weakened linkage between integral transmembrane protein, band 3, and underlying cytoskeleton was observed in mutant mice as the result of reduced high-affinity binding sites provided by ankyrin-1. Hema6 is the only known mouse mutant of Ank1 allelic series that expresses full-length canonical ankyrin-1 at a reduced level, a fact that makes it particularly useful to study the functional impact of ankyrin-1 quantitative deficiency.

Do erythrocytes subjected to cardiopulmonary bypass exhibit changes in their membrane mechanical properties?

Whole blood experiments suggest that cardiopulmonary bypass (CPB) causes red blood cell (RBC) trauma and changes in deformability that may contribute to postoperative microcirculatory dysfunction. We used a novel fluctuation microscopy technique to quantify the effects of CPB on RBC elasticity at a cellular level.

Physicochemical features of dinitrosyl iron complexes with natural thiol-containing ligands underlying the biological activities of these complexes

Current notions and new experimental data of the authors on physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands (glutathione or cysteine), underlying the ability of the complexes to act as NO molecule and nitrosonium ion donors, are considered. This ability determines various biological activities of dinitrosyl iron complexes--inducing long-lasting vasodilation and thereby long-lasting hypotension in human and animals, inhibiting pellet aggregation, increasing red blood cell elasticity, thereby stimulating microcirculation, and reducing necrotic zone in animals with myocardial infarction. Moreover, dinitrosyl iron complexes are capable of accelerating skin wound healing, improving the function of penile cavernous tissue, blocking apoptosis development in cell cultures. When decomposed dinitrosyl iron complexes can exert cytotoxic effect that can be used for curing infectious and carcinogenic pathologies.

Optical Tweezers as a New Biomedical Tool to Measure Zeta Potential of Stored Red Blood Cells

During storage, red blood cells (RBCs) for transfusion purposes suffer progressive deterioration. Sialylated glycoproteins of the RBC membrane are responsible for a negatively charged surface which creates a repulsive electrical zeta potential. These charges help prevent the interaction between RBCs and other cells, and especially among each RBCs. Reports in the literature have stated that RBCs sialylated glycoproteins can be sensitive to enzymes released by leukocyte degranulation. Thus, the aim of this study was, by using an optical tweezers as a biomedical tool, to measure the zeta potential in standard RBCs units and in leukocyte reduced RBC units (collected in CPD-SAGM) during storage. Optical tweezers is a sensitive tool that uses light for measuring cell biophysical properties which are important for clinical and research purposes. This is the first study to analyze RBCs membrane charges during storage. In addition, we herein also measured the elasticity of RBCs also collected in CPD-SAGM. In conclusion, the zeta potential decreased 42% and cells were 134% less deformable at the end of storage. The zeta potential from leukodepleted units had a similar profile when compared to units stored without leukoreduction, indicating that leukocyte lyses were not responsible for the zeta potential decay. Flow cytometry measurements of reactive oxygen species suggested that this decay is due to membrane oxidative damages. These results show that measurements of zeta potentials provide new insights about RBCs storage lesion for transfusion purposes.

Cavitation Bubble Based Measurement of Red Blood Cell Elasticity

We present a novel technique to measure the red blood cell's (RBC) elasticity by exposing RBCs to an impulsive and transient flow. The flow is created from a rapidly expanding laser-induced cavitation bubble. The expanding bubble leads to a stretching deformation of cells close by. The fast flow lasts for approximately 20 microseconds and quickly ceases afterwards. Thereafter the RBCs relax back to their original shape, however on a much slower timescale. This relaxation is studied with high-speed photography and analyzed with digital image processing. In particular we determine the relaxation of the RBC's major and minor axis and find excellent agreement with a power law over several decades. We compare findings on the elasticity of RBCs treated with neuraminidase and confirm the results from the common but much more laborious aspiration method. The figure above depicts the measured strain in linear and logarithmic scaling of treated and untreated RBCs, and a typical relaxation process of a single cell as a function of time. The advantages of this novel technique are its simple implementation and the study of many cells simultaneously.

Precious metals: nanotechnology provides a new dimension

Functionalization of nanoscale (<100 nm) particles at the cellular level is highly specific and can be employed to develop efficient diagnostic and therapeutic procedures with the minimum of side effects. The binding of nanosized particles (quantum dots, iron oxide nanocrystals, nanowires, and nanotubes) with ligands creates varied optical, magnetic, or structural properties through a multivalency effect. These properties determine the affinity and specificity of nanoparticles. Several nanoparticles have been used in biomedicine such as gold, iron oxide, silver, carbon nanotubes, graphene, zinc oxide, alumina, silica, and titanium. Metallic nanoparticles (silver, gold, and silver–gold alloy nanoparticles) with their unique properties play a significant role in the prevention of blood clot formation, dissolution of blood clots, and enhanced imaging of thrombus (blood clot) in vivo. Blood is the biological fluid that delivers nanoparticles to targeted sites. Nanoparticles come in direct contact with all components of the blood, that is, erythrocytes, platelets, and leukocytes. They induce phosphatidylserine on erythrocyte membranes which alter the hemorheological mechanisms. The shape and size of RBCs are particularly important for the efficient transport of oxygen. Furthermore, deformed RBCs can be detected by the elasticity of red blood cells. In this chapter, the focus is on various applications of nanotechnology in biological systems and medicine.

Sickle cell trait should be considered asymptomatic and as a benign condition during physical activity

The following letters are in response to the Point:Counterpoint: “Sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity” that appears in this issue. To the Editor : There is ample evidence for hemorheological abnormalities in

Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Elastic properties of stored red blood cells from sickle trait donor units.

Red blood cells (RBCs) from patients with sickle cell disease present reduced deformability. The aim of this study was to analyse the elasticity of stored RBCs from patients with the sickle cell trait (AS). The cell elasticity was studied, using laser optical tweezers, on storage days 1, 14, 21, 28 and 35. The elasticity of RBC from AS units stored for 1, 14 and 21 days was significantly greater compared with that of control RBC cells stored for the same time-period. More than 30% of the cells from AS units stored for 28 or 35 days were very rigid and escaped from the optical trap. RBCs became rigid during storage, suggesting that haemoglobin S might compromise the cell elasticity.

The use of trental in the complex treatment of patients with chronic pyelonephritis

Studies by a number of authors have revealed significant changes in microcirculation and renal hemodynamics in patients with pyelonephritis. Slowing of capillary blood flow, vasospasm, aggregation of erythrocytes and a decrease in effective renal blood flow were found. These disorders are significantly aggravated after kidney surgery and require corrective treatment. Therefore, along with antibiotics, cardiac glycosides, antispasmodics, antihistamines, we prescribed trental (pentoxifylline), which dilates blood vessels, improves the rheological properties of blood, reduces its viscosity and increases the elasticity of red blood cells.