Stresses at the cell-to-substrate interface during locomotion of fibroblasts.
(17/4621)
Recent technological improvements in the elastic substrate method make it possible to produce spatially resolved measurements of the tractions exerted by single motile cells. In this study we have applied these developments to produce maps of the tractions exerted by 3T3 fibroblasts during steady locomotion. The resulting images have a spatial resolution of approximately 5 micrometers and a maximum intensity of approximately 10(2) kdyn/cm2 (10(4) pN/micrometers2). We find that the propulsive thrust for fibroblast locomotion, approximately 0.2 dyn, is imparted to the substratum within 15 micrometers of the leading edge. These observations demonstrate that the lamellipodium of the fibroblast is able to generate intense traction stress. The cell body and posterior seem to be mechanically passive structures pulled forward entirely by this action. (+info)
Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity.
(18/4621)
We tested the hypothesis that insulin has effects on large artery stiffness in addition to its slow vasodilatory effect on resistance vessels in skeletal muscle, and whether such an effect might be altered in obesity. Eight nonobese (aged 25 +/- 1 years, BMI 22.7 +/- 0.4 kg/m2) and eight obese (aged 27 +/- 2 years, BMI 30.6 +/- 0.9 kg/m2) men were studied under normoglycemic-hyperinsulinemic (sequential 2-h insulin infusions of 1 [step 1] and 2 [step 2] mU x kg(-1) x min(-1)) conditions, and another seven men participated in a saline control study. Central aortic pressure waves were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function every 30 min. This allowed determination of augmentation (the pressure difference between early and late systolic pressure peaks) and the augmentation index (augmentation divided by pulse pressure), a measure of arterial stiffness. Whole-body glucose uptake was reduced by 48 (step 1) and 41% (step 2) (P < 0.01) in the obese subjects versus the nonobese subjects. Basal forearm blood flow averaged 2.5 +/- 0.2 and 2.6 +/- 0.2 ml x dl(-1) x min(-1) in the obese and nonobese subjects, respectively (NS). Insulin induced a significant increase in forearm blood flow after 2.5 h (3.6 +/- 0.4 ml x dl(-1) x min(-1), P < 0.05 vs. basal) in the nonobese subjects and after 4 h in the obese subjects (3.2 +/- 0.2, P < 0.05). In contrast to these slow changes in peripheral blood flow, augmentation and the augmentation index decreased significantly in the nonobese subjects after 1 h (-3.0 +/- 1.6 mmHg and -10.0 +/- 5.4%, respectively, P < 0.001 vs. basal), but remained unchanged until 3 h in the obese subjects. Percent fat (r = 0.86, P < 0.0001) and whole-body glucose uptake (r = -0.72, P < 0.01) correlated with the change in the augmentation index by insulin. These data demonstrate temporal dissociation in insulin's vascular actions. Insulin's effect to decrease arterial stiffness in nonobese subjects (a decrease in wave reflection) is observed under physiological conditions and precedes a slow vasodilatory effect in the periphery. In the obese subjects, insulin's normal effect to decrease central wave reflection is severely blunted. The degree of impairment in this novel vascular action of insulin is closely correlated with the degree of obesity and insulin action on glucose uptake. (+info)
External thoracic restriction, respiratory sensation, and ventilation during exercise in men.
(19/4621)
Multiple factors may contribute to the dyspnea associated with restrictive ventilatory disease (RVD). Simple models that examine specific features of this problem are likely to provide insight into the mechanisms. Previous models of RVD utilizing elastic loads may not represent completely the impact on pulmonary and chest wall receptors derived from breathing at low thoracic volumes. The purpose of this study was to investigate the sensory consequences of breathing at low lung volumes induced by external thoracic restriction in an attempt to further elucidate the etiology of dyspnea in this setting. Ten men were studied, with and without an inelastic corset applied at residual volume (restriction resulted in mean reductions in vital capacity, functional residual capacity, residual volume, and forced expired volume in 1 s of 44, 31, 12.5, and 42%, respectively). During 10-min steady-state exercise tests (at a workload set to achieve approximately 65% maximum heart rate), restriction resulted in significant increases, compared with control, in minute ventilation (61 vs. 49 l/min), respiratory frequency (43 vs. 23 breaths/min), and visual analog scale measurements of respiratory discomfort (65 vs. 20 mm). Alveolar hyperventilation (end-tidal PCO2 = 39 vs. 44 Torr for control) and mild O2 desaturation (arterial blood O2 saturation = 93 vs. 95% for control) occurred. Hypoxemia, atelectasis, increased work and effort of breathing, or a decrease in the volume-related feedback from chest wall and/or lungs could be responsible for the increased dyspnea reported. External thoracic restriction provides a useful model to study mechanisms of dyspnea in RVD. (+info)
The role of radial elastic properties in the development of aortic dissections.
(20/4621)
PURPOSE: The response of the upper and lower thoracic aorta to radial tensile stresses was compared with the response to circumferential and longitudinal stresses to understand the role of tensile stress in the tearing phase of an aortic dissection. METHODS: Square tissue samples (1.6 by 1.6 cm) were cut from the upper and lower segments of six porcine thoracic aortas and were elongated in the radial direction with a tensile testing machine. The radial extensibility of the thoracic aorta was compared with adjacent tissue samples that were tested in tension in the circumferential and longitudinal directions based on Young's modulus (ie, the ratio of tensile stress to strain). RESULTS: The elastic properties of the thoracic aorta in the radial direction were markedly different from both the circumferential and longitudinal properties. The average Young's modulus (calculated immediately before failing) was significantly lower in the radial direction for both the upper and lower thoracic segments (61.4 +/- 4.3 kPa, SEM) than the Young's modulus of corresponding segments in the circumferential and longitudinal directions that were not tested to failure (151.1 +/- 8.6 kPa and 112.7 +/- 9.2 kPa, respectively; P <. 05). Sections 7 micrometer thick were collected from four samples obtained from one upper thoracic aorta that were strained at 0, 1.0, 2.5, and 4.0 and then stained either with Movat's pentachrome or with hematoxylin and eosin. Histological analysis of the samples stressed in the radial direction revealed that smooth muscle cells were torn loose from their attachments to each other and to adjacent elastin. CONCLUSION: Although the aorta normally functions under radial compressive stresses associated with lumen blood pressure, these results show that the aorta tears radially at a much lower value of stress than would have been predicted from previous studies that have reported longitudinal and circumferential Young's modulus. This could explain why dissections propagate readily once the initial tear occurs. (+info)
Structural, functional, and hemodynamic changes of the common carotid artery with age in male subjects.
(21/4621)
Aging of the common carotid artery (CCA) is associated with different principal structural, functional, and hemodynamic changes, which are often influenced by several atherosclerotic risk factors, so that it is difficult to estimate the exclusive effect of aging on this process. Studies dealing with vascular aging of the CCA usually assess only single, dimensional, or functional parameters, although it is likely that there are interactions and probably differences between them. Moreover, regional vascular blood flow characteristics are often not taken into consideration. Therefore, the aim of the study was to assess the age-related multiparametric changes of the CCA properties with ultrasound in 69 male subjects between the ages of 16 and 75 (42.4+/-16.5 years), who were screened for the absence of major atherosclerotic risk factors or existing vascular disease. As a result, the intima media thickness (0.052 mm/10 y) and diastolic diameter (0.17 mm/10 y) increased nearly linearly with age (r=0.60, P<0.001; and r=0.46, P<0.001, respectively). The absolute diastolic/systolic diameter change diminished by 0.10 mm/10 y (r=-0. 73, P<0.001) and peak expansion velocity dropped by 0.12 cm/s per 10 years (r=-0.62, P<0.001) highly significantly with age. The peak blood flow velocity decreased continuously with age (r=-0.67, P<0. 00) by 9.3 cm/s per 10 years. According to multiple regression analysis, peak blood flow velocity seems to reflect the changes of several structural and functional parameters in one; intima-media thickness was determined by diastolic arterial diameter and age as independent variables. The data indicate that a multiparametric assessment may contribute to a better understanding of vascular aging and might be the basis for further studies to evaluate the association of atherosclerotic risk factors and/or major vascular disease with local changes in the CCA. (+info)
High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate.
(22/4621)
We have developed a new approach to detect mechanical forces exerted by locomoting fibroblasts on the substrate. Cells were cultured on elastic, collagen-coated polyacrylamide sheets embedded with 0. 2-micrometer fluorescent beads. Forces exerted by the cell cause deformation of the substrate and displacement of the beads. By recording the position of beads during cell locomotion and after cell removal, we discovered that most forces were radially distributed, switching direction in the anterior region. Deformations near the leading edge were strong, transient, and variable in magnitude, consistent with active local contractions, whereas those in the posterior region were weaker, more stable, and more uniform, consistent with passive resistance. Treatment of cells with cytochalasin D or myosin II inhibitors caused relaxation of the forces, suggesting that they are generated primarily via actin-myosin II interactions; treatment with nocodazole caused no immediate effect on forces. Immunofluorescence indicated that the frontal region of strong deformation contained many vinculin plaques but no apparent concentration of actin or myosin II filaments. Strong mechanical forces in the anterior region, generated by locally activated myosin II and transmitted through vinculin-rich structures, likely play a major role in cell locomotion and in mechanical signaling with the surrounding environment. (+info)
Elasticity measurements show the existence of thin rigid cores inside mitotic chromosomes.
(23/4621)
Chromosome condensation is one of the most critical steps during cell division. However, the structure of condensed mitotic chromosomes is poorly understood. In this paper we describe a new approach based on elasticity measurements for studying the structure of in vitro assembled mitotic chromosomes in Xenopus egg extract. The approach is based on a unique combination of measurements of both longitudinal deformability and bending rigidity of whole chromosomes. By using specially designed micropipettes, the chromosome force-extension curve was determined. Analysis of the curvature fluctuation spectrum allowed for the measurement of chromosome bending ridigity. The relationship between the values of these two parameters is very specific: the measured chromosome flexibility was found to be 2,000 times lower than the flexibility calculated from the experimentally determined Young modulus. This requires the chromosome structure to be formed of one or a few thin rigid elastic axes surrounded by a soft envelope. The properties of these axes are well-described by models developed for the elasticity of titin-like molecules. Additionally, the deformability of in vitro assembled chromosomes was found to be very similar to that of native somatic chromosomes, thus demonstrating the existence of an essentially identical structure. (+info)
Lung and chest wall mechanics in ventilated patients with end stage idiopathic pulmonary fibrosis.
(24/4621)
BACKGROUND: Idiopathic pulmonary fibrosis is an inflammatory disease which leads to chronic ventilatory insufficiency and is characterised by a reduction in pulmonary static and dynamic volumes. It has been suggested that lung elastance may also be abnormally increased, particularly in end stage disease, but this has not been systematically tested. The aim of this study was to assess the respiratory mechanics during mechanical ventilation in patients affected by end stage disease. METHODS: Respiratory mechanics were monitored in seven patients with idiopathic pulmonary fibrosis being ventilated for acute respiratory failure (PaO2/FiO2 5.8 (0.3); pH 7. 28 (0.02); PaCO2 8.44 (0.82) kPa; tidal volume 3.4 (0.2) ml/kg; respiratory rate 35.1 (8.8) breaths/min) using an oesophageal balloon and airway occlusion during constant flow inflation. The total respiratory system mechanics (rs) was partitioned into lung (L) and chest wall (w) mechanics to measure static intrinsic positive end expiratory pressure (PEEPi), static (Est) and dynamic (Edyn) elastances, total respiratory resistance (Rrs), interrupter respiratory resistance (Rint,rs), and additional respiratory resistance (DeltaRrs). RESULTS: PEEPi was negligible in all patients. Edyn,rs and Est,rs were markedly increased (60.9 (7.3) and 51.9 (8. 0) cm H2O/l, respectively), and this was due to abnormal lung elastance (dynamic 53.9 (8.0) cm H2O/l, static 46.1 (8.1) cm H2O/l) while chest wall elastance was only slightly increased. Rrs and Rint, rs were also increased above the normal range (16.7 (4.5) and 13.7 (3.5) cm H2O/l/s, respectively). RL and Rint,L contributed 88% and 89%, on average, to the total. Edyn,rs, Est,rs, Rrs and Rint,rs were significantly correlated with the degree of hypercapnia (r = 0.64 (p<0.01), r = 0.54 (p<0.05), r = 0.84 (p<0.001), and r = 0.72 (p<0. 001), respectively). CONCLUSIONS: The elastances and resistances of the respiratory system are significantly altered in ventilated patients with end stage idiopathic pulmonary fibrosis. These features are almost totally due to abnormalities in lung mechanics. These profound alterations in elastic and resistive mechanical properties at this stage of the disease may be responsible for the onset of hypercapnia. (+info)