Deformability Of Human Red Blood Cells Research Articles

Recovery time course of erythrocyte deformability following exposure to shear is dependent upon conditioning shear stress.

Red blood cell (RBC) deformability may increase, or decrease, following application of shear stress ("shear conditioning"), depending upon the specific magnitude and duration of exposure. However, the time course of altered RBC deformability following shear remains unresolved. We utilised shear conditioning known to increase (10 Pa) or decrease (64 Pa) RBC deformability and subsequently rested the cells; serial measurements of deformability during the rest period facilitated defining the time course of recoverability. A second experiment repeated the shear conditioning and recovery period to explore whether multiple duty-cycles augmented the response following the initial exposure. Shear conditioning was performed for 300 s at the desired shear stress. Ektacytometry was used to quantify human RBC deformability immediately and during rest (3, 5, 60, 120, 240, 300 s) using discrete samples. RBC were shear conditioned twice in a separate experiment, with 300 s rest separating the conditioning. Shear conditioning at 10 Pa induced increased cell deformability by 19.5 ± 0.3%, which reduced to 7.2 ± 0.4% after 300 s of rest. Shear conditioning at 64 Pa decreased cell deformability by 30.5 ± 13.9%, and after 300 s rest, remained decreased (19.3 ± 9.4%) compared with baseline. The second duty-cycle augmented initial responses induced by shear conditioning. Specific shear conditioning results in either temporarily increased cell deformability, or a less reversible decrease of RBC deformability.

2013 Bower Award and Prize for Achievement in Science presented to Kenichi Iga, Tokyo Institute of Technology, Tokyo, Japan

The mechanical behavior of materials can be modeled and evaluated across multiple scales that encompass: atomic and molecular rearrangements to create incipient defect nuclei; combination or growth of such nuclei to form micro-scale and subsequently macro-scale defects; and finally development of critical flaw sizes that result in final failure of engineering structures. Through an understanding of the mechanisms governing these processes, which depend on the loading conditions and the specific materials, new or modified materials systems designs can be integrated with advanced structural concepts to advance our energy, civil, transportation and healthcare infrastructures, among others.Subra Suresh׳s research includes development of novel experimental techniques and the discovery of new mechanistic processes that are broadly applicable to essentially every major class of natural and synthetic materials, including metals, ceramics, polymers, composites, biomolecules and biological cells. Beginning in the 1970s, he elucidated mechanisms of near-threshold fatigue crack growth in steels and aluminum alloys, contributing to improved alloy design for nuclear pressure vessels, fossil plants, offshore structures and aircraft. Subsequent work identified mechanisms for toughening brittle ceramics against fatigue crack growth under cyclic compressive loads. Turning to the microscale and the study of thin films, he developed new methods for extracting elastoplastic and functional properties of materials from small-volume contact probing. This led to new theories, computation and experiments on material and surface design through controlled gradients in composition and properties, and applications to coatings. At the nanoscale, he experimentally discovered nanocrystallization of bulk amorphous alloys during nanoindentation, and also showed how nanoscale twins could optimize the strength and ductility of fine grained metals. Most recently, he is noted for demonstrating the effects of disease-induced changes to human red blood cell deformability and biorheology, and for linking these changes to human diseases such as malaria.

2013 Benjamin Franklin Medal in Mechanical Engineering presented to Subra Suresh

The mechanical behavior of materials can be modeled and evaluated across multiple scales that encompass: atomic and molecular rearrangements to create incipient defect nuclei; combination or growth of such nuclei to form micro-scale and subsequently macro-scale defects; and finally development of critical flaw sizes that result in final failure of engineering structures. Through an understanding of the mechanisms governing these processes, which depend on the loading conditions and the specific materials, new or modified materials systems designs can be integrated with advanced structural concepts to advance our energy, civil, transportation and healthcare infrastructures, among others.Subra Suresh׳s research includes development of novel experimental techniques and the discovery of new mechanistic processes that are broadly applicable to essentially every major class of natural and synthetic materials, including metals, ceramics, polymers, composites, biomolecules and biological cells. Beginning in the 1970s, he elucidated mechanisms of near-threshold fatigue crack growth in steels and aluminum alloys, contributing to improved alloy design for nuclear pressure vessels, fossil plants, offshore structures and aircraft. Subsequent work identified mechanisms for toughening brittle ceramics against fatigue crack growth under cyclic compressive loads. Turning to the microscale and the study of thin films, he developed new methods for extracting elastoplastic and functional properties of materials from small-volume contact probing. This led to new theories, computation and experiments on material and surface design through controlled gradients in composition and properties, and applications to coatings. At the nanoscale, he experimentally discovered nanocrystallization of bulk amorphous alloys during nanoindentation, and also showed how nanoscale twins could optimize the strength and ductility of fine grained metals. Most recently, he is noted for demonstrating the effects of disease-induced changes to human red blood cell deformability and biorheology, and for linking these changes to human diseases such as malaria.

P126 - Influence of chronic endurance exercise on human red blood cell deformability

P126 - Influence of chronic endurance exercise on human red blood cell deformability

Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel

It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the centerline of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases.

B213 毛細血管を模擬したマイクロチャンネルアレイを流れる赤血球の変形の可視化

It is the first step to proper appreciation of human cardiovascular system to clarify the microcirculatory blood flow. Especially, because of red blood cell (RBC) play an indispensable role in mass and gas transfer in capillary vessel, it is important to make clear the behavior of RBC in capillary. And it is well know that. RBC passes through capillary whose diameter is smaller than that of RBC with small pressure gradients. In this study, new micro-channel array devices which are able to adaptt to evaluating both the throughput of whole blood and the deformability of RBC are developed. The micro channel array has been fabricated using the semiconductor fabrication technique. The micro channel is 5.2μm width×5.0μm height and either 100μm or 300μm in length. Using fabricated micro channel array chip, deformation of human RBC is visualized.

Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways.

To investigate the mechanism of the regulation of human red blood cell deformability, we examined the deformability under mechanical stress. Washed human red blood cells were rapidly injected through a fine needle, and their filterability was measured using a nickel mesh filter. The decrease in filterability showed a V-shaped curve depending on the extracellular Ca2+ concentration; the maximum decrease was achieved at approximately 50 muM. The decreased filterability was accompanied by no change in cell morphology and cell volume, indicating that the decrease in filterability can be ascribed to alterations of the membrane properties. Ca2+ entry blockers (nifedipine and felodipine) inhibited the impairment of filterability under mechanical stress. Prostaglandins E1 and E2, epinephrine, and pentoxifylline, which are thought to modulate the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) level of red blood cells, improved or worsened the impaired filterability according to their expected actions on the cAMP level of the cells. These results strongly suggest that the membrane properties regulating red blood cell deformability are affected by the signal transduction system, including Ca(2+)-dependent and cAMP-mediated signaling pathways.

Effect of acute smoking on red blood cell deformability in healthy young and elderly non-smokers, and effect of verapamil on age- and acute smoking-induced change in red blood cell deformability.

The effects of age and acute smoking on red blood cell (RBC) deformability in non-smokers have been studied. RBC ATP levels and in vitro effects of verapamil on pre- and post-smoking filterabilities have been determined in an attempt to make an approach to the mechanism(s) responsible for the effect of age and acute smoking on RBC deformability. Nine young and nine elderly healthy non-smokers volunteered to the study. Venous blood samples obtained before and after the smoking of one cigarette, were used for ATP analysis and RBC deformability determination. ATP was determined enzymatically, deformability was assessed by gravity driven microfiltration technique. Verapamil was added to pre- and post-smoking blood samples to yield a final concentration of 1 mg-1. RBC deformability was found to decrease in the elderly group by 19.1% of that of the young group (p < 0.001). Acute smoking decreased the filterabilities of RBCs by 15.3% (p < 0.0001) and 15.9% (p < 0.001) of their pre-smoking values in the young and the elderly groups respectively. The smoking-induced decreases in RBC deformability were found to be associated with slight but significant decreases (p < 0.02 and p < 0.005 for the young and the elderly group respectively) in RBC ATP concentrations. Ca2+ channel blockade with verapamil did not produce any significant change in pre- and post-smoking filterabilities of RBCs from the young group, but improved these variables by 9.7% (p < 0.005) and 10.7% (p < 0.05) in the elderly group. In conclusion age and smoking are two independent factors that affect the deformability of human RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)