Narrow Results

In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

Bladder control problems affect both men and women and range from an overactive bladder, to urinary incontinence, to bladder obstruction and cancer. These disorders affect more than 200 million people worldwide. Loss of bladder function significantly affects the quality of life, both physically and psychologically, and also has a large impact on the healthcare system, i.e., the incurring costs related to diagnosis, treatment and medical/nursing care. Improvements in diagnostic capabilities and disease management are essential to improve patient care and quality of life and reduce the economic burden associated with bladder disorders. This paper summarizes some of the key contributions to understanding the mechanics of the bladder ranging from work conducted in the 1970s through the present time with a focus on material testing and theoretical modeling. Advancements have been made in these areas and a significant contribution to these changes was related to technological improvements.

The subcellular location of β-catenin and N-cadherin in cultured bovine endothelial cells (ECs) exposed to hydrostatic pressure was investigated. ECs were exposed to physiological blood pressure under a hydrostatic head of culture medium for 24 hours. Pressured ECs exhibited changes in morphology and proliferation. Immunofluorescent localization of β-catenin and N-cadherin indicated changes in their distribution in pressured compared to control cells, β-catenin was located at the cell membrane in control cells but in the cytoplasm and nucleus of pressured cells. In contrast, N-cadherin was associated with the cell membrane in pressure cells. Changes in the location of these two proteins in ECs have previously been associated with increase proliferation and changes in cell morphology. Therefore the hydrostatic pressure induced changes in these may be mediated, in part, by β-catenin and N-cadherin.

The purpose of this study was to reveal circumferential strain distributions in aortas by using a newly designed observation technique. Six cylindrical descending thoracic aortas were excised from Japanese white rabbits and stretched in the longitudinal direction to their in vivo length. Five-millimeter long needles (φ 0.4 mm) were penetrated into the aorta as a marker of circumferential displacement of the aorta. During application of internal pressure ranging from 0 to 200 mmHg, displacements of needles were recorded with a CCD camera from longitudinal direction of the aorta and with other two CCD cameras from both lateral sides of aorta. The images of cameras were used to determine the penetration points of all needles. From the penetration points, we calculated the local circumferential lengths of aorta and circumferential local stretch ratios. As a result, circumferential stretch ratio of ventral side of aorta was significantly higher than that of dorsal side (p < 0.05). This result suggests that nonuniform strain distributions exist in the circumferential direction of aortas. The present method was useful to measure the detailed mechanical property of blood vessels and to understand vascular mechanics.

We construct numerical aneurysm models arisen from both straight and curved arteries, under the hypothesis that high local wall shear stress larger than a certain threshold value will lead to a linear decrease in the wall mechanical properties. Development of aneurysm is observed in both the straight and curved models. In the straight model, the growth of aneurysm is small and only at the distal neck region, and the aneurysm stops growing after several steps. In contrast, in the curved model, the aneurysm continues to grow in height and width. Our computer simulation study shows that even if the wall shear stress inside an aneurysm is low, aneurysm development can occur due to degeneration of the wall distal and proximal to the aneurysm. The interaction between the hemodynamic change (caused by the shape change) and the wall degeneration is key to the development of aneurysms. Our method demonstrates the potential utility of rule-based numerical methods in the investigation of developmental biology of cardiovascular diseases.