scholarly journals A Bistable Mechanism Mediated by Integrins Controls Mechanotaxis of Leukocytes

2018 ◽  
Author(s):  
Alexander Hornung ◽  
Thomas Sbarrato ◽  
Nicolas Garcia-Seyda ◽  
Laurene Aoun ◽  
Xuan Luo ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Relative Number ◽  
Cellular Level ◽  
Bistable System ◽  
Mechanical Stimuli ◽  
Cell Orientation ◽  
Complete Chain ◽  
Controlling Parameter ◽  
No Signaling ◽  
Bistable Mechanism

AbstractThe recruitment of leukocytes from blood vessels to inflamed zones is guided by biochemical and mechanical stimuli, with mechanisms only partially deciphered. We studied here the guidance by flow of primary human effector T lymphocytes crawling on substrates coated with ligands of integrins LFA-1 (αLβ2) and VLA-4 (α4β1), and showed that cells segregated in two populations of opposite orientation for combined adhesion. Sharp decisions of orientation were shown to rely on a bistable mechanism between LFA-1-mediated upstream and VLA-4-dominant downstream phenotypes. At the molecular level, bistability results from a differential front-rear polarization of both integrins affinity, combined with an inhibiting crosstalk of LFA-1 toward VLA-4. At the cellular level, directivity with or against the flow is mechanically mediated by the passive orientation of detached uropod or lamellipod by flow. This complete chain of logical events provides a unique mechanistic picture of a guiding mechanism, from stimuli to cell orientation.SignificanceCellular guidance is crucial to many biological functions, but the precise mechanisms remain unclear. We have analyzed here an original phenotype of flow-guided cells mimicking leukocytes crawling into the blood vessels and showed that thecontrolling parameterof cells decision to migrate upstream or downstream was therelative numberof two specific adhesion molecules, the integrins LFA-1 and VLA-4. The spatial polarisation of integrins affinity and an intermutually feedback of their activation create a bistable system where cells adhere either by their tip or their tail and orient respectively downstream or upstream. This mechanism therefore proposes a complete chain of event from stimuli to cell orientation and differs strongly from the chemotaxis paradigm because stimuli trigger no signaling.

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Cell Interactions ◽  
Aortic Aneurysms ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Matrix Cell

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization

2005 ◽  
Vol 98 (6) ◽  
pp. 2381-2389 ◽  
Author(s):  
A. Reich ◽  
N. Jaffe ◽  
A. Tong ◽  
I. Lavelin ◽  
O. Genina ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Growth Plate ◽  
Developmental Process ◽  
Mechanical Strain ◽  
Cell Counting ◽  
Mechanical Stimuli ◽  
Growth Plates ◽  
Average Width ◽  
The Matrix ◽  
Weight Loading

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 ± 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

scholarly journals Enhancement of a 3-DOF submerged wave energy device using bistability

2020 ◽  
Vol 3 (2) ◽  
pp. 73-82
Author(s):  
Benjamin Schubert ◽  
William S. P. Robertson ◽  
Benjamin S. Cazzolato
Keyword(s):  
Wave Energy ◽  
Degrees Of Freedom ◽  
Phase Relationship ◽  
Bistable System ◽  
Viscous Drag ◽  
Regular Waves ◽  
Point Absorber ◽  
Exciting Forces ◽  
Bistable Mechanism ◽  
The Impact

The dynamic response of a submerged CETO shaped quasi-point absorbing wave energy converter coupled to a bistable power take off is presented in this study. Whilst the impact of bistability has been shown in a limited number of situations to improve the amount of power generated, many models have been restricted to a single degree of freedom and often ignore drag effects. To overcome these model limitations, a submerged single tether point absorber with a bistable power take off was modelled using both 1 and 3 degrees of freedom. The device was subjected to regular waves and included a simple model of viscous drag. The bistable mechanism was provided by a magnetic dipole model quantified by a dimensionless parameter applicable to any bistable system. The performance of the device was is assessed by the theoretical power generated. Over each model, the previously observed benefit of bistability was not consistently obtained. Simulations of regular waves demonstrated an increase in generated power for suboptimal conditions for some frequencies, while a reduction in generated power was observed in optimal conditions. The performance increase showed strong correlation to the phase relationship between the motion and exciting forces as a result of bistability.

Heat Transfer to Blood Vessels

1980 ◽  
Vol 102 (2) ◽  
pp. 110-118 ◽  
Author(s):  
J. C. Chato
Keyword(s):  
Heat Transfer ◽  
Blood Vessels ◽  
Internal Heat ◽  
Absolute Magnitude ◽  
Skin Surface ◽  
Tissue Temperature ◽  
Single Vessel ◽  
Controlling Parameter ◽  
Order Of Magnitude ◽  
Linear Effects

Heat transfer to individual blood vessels has been investigated in three configurations: a single vessel, two vessels in counterflow, and a single vessel near the skin surface. For a single vessel the Graetz number is the controlling parameter. The arterioles, capillaries, and venules have very low Graetz numbers, Gz < 0.4, and act as perfect heat exchangers in which the blood quickly reaches the tissue temperature. The large arteries and veins with Graetz numbers over 103 have virtually no heat exchange with the tissue, and blood leaves them at near the entering temperature. Heat transfer between parallel vessels in counterflow is influenced most strongly by the relative distance of separation and by the mass transferred from the artery to the vein along the length. These two effects are of the same order of magnitude, whereas the film coefficients in the blood flow are of significant but lesser importance. The effect of a blood vessel on the temperature distribution of the skin directly above it and on the heat transfer to the environment increases with decreasing depth-to-radius ratio and decreasing Biot number based on radius. The absolute magnitude of these effects is independent of other linear effects, such as internal heat generation or a superimposed one-dimensional heat flux.

Theory and Experiments for Mechanically-Induced Remodeling of Tissue Engineered Blood Vessels

2008 ◽  
Vol 57 ◽  
pp. 226-234 ◽  
Author(s):  
Rudolph L. Gleason ◽  
William Wan
Keyword(s):  
Mechanical Properties ◽  
Blood Vessels ◽  
Laser Scanning ◽  
Biomechanical Testing ◽  
Small Diameter ◽  
Mechanical Stimuli ◽  
Two Photon ◽  
Constrained Mixture ◽  
Tissue Engineered Blood Vessels ◽  
Luminal Flow

There is a great unmet clinical need to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune response and suitable mechanical properties. In this paper we describe experimental and computational frameworks to characterize the use of mechanical stimuli to improve the mechanical properties of TEBVs. We model the TEBV as a constrained mixture and track the production, degradation, mechanical state, and organization of each structural constituent. Specifically, we assume that individual load bearing constituents can co-exist within each neighborhood and, although they are constrained to deform together, each constituent within this neighborhood may have different natural (i.e., stress-free) configurations. Motivated by this theoretical framework, we have designed a bioreactor and biomechanical testing device for TEBVs. This device is designed to provide precise and independent control of mean and cyclic luminal flow rate, transmural pressure, and axial load over weeks and months in culture and perform intermittent biaxial biomechanical tests. This device also fits under a two-photon laser scanning microscope for 3-dimenstional imaging of the content and organization of cells and matrix constituents. These data directly support our theoretical model.

scholarly journals Metal effects on histological and biochemical parameters of common rudd (Scardinius erythrophthalmus L.)

2014 ◽  
Vol 22 (3) ◽  
pp. 197-206 ◽  
Author(s):  
Elenka Georgieva ◽  
Stela Stoyanova ◽  
Iliana Velcheva ◽  
Tonka Vasileva ◽  
Veselin Bivolarski ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Morphological Structure ◽  
Fatty Degeneration ◽  
Cellular Level ◽  
Fish Liver ◽  
Metal Concentrations ◽  
Scardinius Erythrophthalmus ◽  
Different Seasons ◽  
Permissible Levels ◽  
The Common

Abstract The present study aimed to evaluate the current contamination status of Topolnitsa Reservoir, which is located in a region with intensive copper mining. The reservoir has been continually contaminated with metals over the last few decades. As, Cd, Cu, Ni, Pb, and Zn concentrations were measured in surface water samples and in the liver of common rudd, Scardinius erythrophthalmus (L.), in three different seasons: spring, summer, and autumn. The morphological structure of the fish liver was examined and the hepatic LDH, ALAT, and ASAT activities were measured. In general, metal concentrations in the water varied, but As and Cu were present in all three seasons at levels higher than the maximum permissible levels set by law. The metal concentrations in the fish liver were significantly higher than in the water. Histological alterations were classified as degenerative changes (granular, vacuolar, hydropic, and fatty degeneration), necrotic changes (necrobiosis) - karyopyknosis, karryorehsis, and karyolyzis, and necrosis)); and changes in blood vessels (hyperemia in sinusoids and major blood vessels). Higher LDH, ALAT, and ASAT activities in fish livers were measured in comparison to reference fish. In addition, the ALAT activity in the livers of S. erythrophthalmus from Topolnitsa Reservoir was significantly higher in the summer. Overall, it can be concluded that the metal-contaminated waters of Topolnitsa Reservoir lead to negative changes in the common rudd tissues at the cellular level including impaired structure and enhanced enzymatic activity in the fish liver.

scholarly journals Basis of the general theory of pathology (Part 4. "Atherosclerosis" or "Scleroatherosis"?)

2019 ◽  
pp. 3-12
Author(s):  
V. S. Prokopchook ◽  
A. V. Lyckbäck
Keyword(s):  
Blood Vessels ◽  
Healthy Lifestyle ◽  
Fatty Degeneration ◽  
Cellular Level ◽  
The Other ◽  
Sequence Of Events ◽  
The One ◽  
Second Period ◽  
Main Factor

This is not a play on words, but a key to solving a problem that has been deadlocked. The science of atherosclerosis is still based on the experiments of N. N. Anichkov. It always prioritizes lipid infiltration of vessel's walls. In fact, the lipid infiltration of the vessel's walls is not related to the origin of lipids in atheromas. Their origin is always associated with fatty degeneration of myofibroblasts in places of sclerosis (fibrous plaques), but not with hematogenous infiltration. The key to solving this problem lies in a disclosure of the genesis of sclerotic changes in intima. On the one hand it concerns a primary age sclerosis (compensatory) as well as secondary sclerosis (inflammatory, etc). On the other hand it is important to establish causes of degradation (fatty degeneration) and death of myofibroblasts (the so-called Langgans'cells) in places of sclerosis (fibrous plaques), followed by atheroma formation. We have first showed in vivo (at the cellular level) that a death of myofibroblasts in plaques with following release of lipids occurs due to the fact that these myofibroblasts reach the Heiflik's limit much faster than myofibroblasts on healthy vessels. These occurs due to shortening of telomeres in myofibroblasts that intensively multiply in places of reparative sclerosis. The authors propose replacing the term “atherosclerosis” with “scleroatherosis”, which more accurately reflects the essence of the disease and the sequence of events in its pathogenesis. Considering "scleroarethosis" as a nosological form, two periods of development of the process should be emphasized: the first – sclerotic period (compensatory) and the second – atheromatous (period of decompensation). The second period is accompanied by all manifestations and complications known for scleroatherosis that can't be eliminated. It is no need to spend billions on senseless "purifying” blood vessels and "lowering" cholesterol in blood plasma. It is more important to focus on a healthy lifestyle and, above all, to fight with arterial hypertension as with a main factor of blood vessels' deterioration.

Effect of Combined Cyclic Stretch and Fluid Shear Stress on Endothelial Cell Morphological Responses

2005 ◽  
Vol 127 (3) ◽  
pp. 374-382 ◽  
Author(s):  
Tomas B. Owatverot ◽  
Sara J. Oswald ◽  
Yong Chen ◽  
Jeremiah J. Wille ◽  
Frank C-P Yin
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Time Course ◽  
Fluid Shear Stress ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Cell Orientation ◽  
Fluid Shear ◽  
Aortic Endothelial Cells

Endothelial cells in vivo are normally subjected to multiple mechanical stimuli such as stretch and fluid shear stress (FSS) but because each stimulus induces magnitude-dependent morphologic responses, the relative importance of each stimulus in producing the normal in vivo state is not clear. Using cultured human aortic endothelial cells, this study first determined equipotent levels of cyclic stretch, steady FSS, and oscillatory FSS with respect to the time course of cell orientation. We then tested whether these levels of stimuli were equipotent in combination with each other by imposing simultaneous cyclic stretch and steady FSS or cyclic stretch and oscillatory FSS so as to reinforce or counteract the cells’ orientation responses. Equipotent levels of the three stimuli were 2% cyclic stretch at 2%∕s, 80dynes∕cm2 steady FSS and 20±10dynes∕cm2 oscillatory FSS at 20dyne∕cm2-s. When applied in reinforcing fashion, cyclic stretch and oscillatory, but not steady, FSS were additive. Both pairs of stimuli canceled when applied in counteracting fashion. These results indicate that this level of cyclic stretch and oscillatory FSS sum algebraically so that they are indeed equipotent. In addition, oscillatory FSS is a stronger stimulus than steady FSS for inducing cell orientation. Moreover, arterial endothelial cells in vivo are likely receiving a stronger stretch than FSS stimulus.

scholarly journals Mechanical factors contributing to the Venus flytrap’s rate-dependent response to stimuli

2021 ◽  
Author(s):  
Eashan Saikia ◽  
Nino F. Läubli ◽  
Hannes Vogler ◽  
Markus Rüggeberg ◽  
Hans J. Herrmann ◽  
...  
Keyword(s):  
Fluid Transport ◽  
Angular Displacement ◽  
Mechanical Stimulus ◽  
Cellular Level ◽  
Sensory Cells ◽  
Mechanical Stimuli ◽  
Multi Scale ◽  
Rate Dependent ◽  
Dionaea Muscipula ◽  
Mechanical Factors

AbstractThe sensory hairs of the Venus flytrap (Dionaea muscipula Ellis) detect mechanical stimuli imparted by their prey and fire bursts of electrical signals called action potentials (APs). APs are elicited when the hairs are sufficiently stimulated and two consecutive APs can trigger closure of the trap. Earlier experiments have identified thresholds for the relevant stimulus parameters, namely the angular displacement $$\theta $$ θ and angular velocity $$\omega $$ ω . However, these experiments could not trace the deformation of the trigger hair’s sensory cells, which are known to transduce the mechanical stimulus. To understand the kinematics at the cellular level, we investigate the role of two relevant mechanical phenomena: viscoelasticity and intercellular fluid transport using a multi-scale numerical model of the sensory hair. We hypothesize that the combined influence of these two phenomena and $$\omega $$ ω contribute to the flytrap’s rate-dependent response to stimuli. In this study, we firstly perform sustained deflection tests on the hair to estimate the viscoelastic material properties of the tissue. Thereafter, through simulations of hair deflection tests at different loading rates, we were able to establish a multi-scale kinematic link between $$\omega $$ ω and the cell wall stretch $$\delta $$ δ . Furthermore, we find that the rate at which $$\delta $$ δ evolves during a stimulus is also proportional to $$\omega $$ ω . This suggests that mechanosensitive ion channels, expected to be stretch-activated and localized in the plasma membrane of the sensory cells, could be additionally sensitive to the rate at which stretch is applied.

scholarly journals A Phenomenological Model for Mechanically Mediated Growth, Remodeling, Damage, and Plasticity of Gel-Derived Tissue Engineered Blood Vessels

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Julia Raykin ◽  
Alexander I. Rachev ◽  
Rudolph L. Gleason
Keyword(s):  
Blood Vessels ◽  
Damage Mechanics ◽  
Time Course ◽  
Material Behavior ◽  
Published Data ◽  
Mechanical Stimuli ◽  
Volumetric Growth ◽  
Model Framework ◽  
Modeling Framework ◽  
Tissue Engineered Blood Vessels

Mechanical stimulation has been shown to dramatically improve mechanical and functional properties of gel-derived tissue engineered blood vessels (TEBVs). Adjusting factors such as cell source, type of extracellular matrix, cross-linking, magnitude, frequency, and time course of mechanical stimuli (among many other factors) make interpretation of experimental results challenging. Interpretation of data from such multifactor experiments requires modeling. We present a modeling framework and simulations for mechanically mediated growth, remodeling, plasticity, and damage of gel-derived TEBVs that merge ideas from classical plasticity, volumetric growth, and continuum damage mechanics. Our results are compared with published data and suggest that this model framework can predict the evolution of geometry and material behavior under common experimental loading scenarios.

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