共查询到20条相似文献,搜索用时 31 毫秒
1.
Vascular endothelial cells are located at the innermost layer of the blood vessel wall and are always exposed to three different mechanical forces: shear stress due to blood flow, hydrostatic pressure due to blood pressure and cyclic stretch due to vessel deformation. It is well known that endothelial cells respond to these mechanical forces and change their shapes, cytoskeletal structures and functions. In this review, we would like to mainly focus on the effects of shear stress and hydrostatic pressure on endothelial cell morphology. After applying fluid shear stress, cultured endothelial cells show marked elongation and orientation in the flow direction. In addition, thick stress fibers of actin filaments appear and align along the cell long axis. Thus, endothelial cell morphology is closely related to the cytoskeletal structure. Further, the dynamic course of the morphological changes is shown and the related events such as changes in mechanical stiffness and functions are also summarized. When endothelial cells were exposed to hydrostatic pressure, they exhibited a marked elongation and orientation in a random direction, together with development of centrally located, thick stress fibers. Pressured endothelial cells also exhibited a multilayered structure with less expression of VE-cadherin unlike under control conditions. Simultaneous loading of hydrostatic pressure and shear stress inhibited endothelial cell multilayering and induced elongation and orientation of endothelial cells with well-developed VE-cadherin in a monolayer, which suggests that for a better understanding of vascular endothelial cell responses one has to take into consideration the combination of the different mechanical forces such as exist under in vivo mechanical conditions. 相似文献
2.
Vascular walls change their dimensions and mechanical properties adaptively in response to blood pressure. Because these responses are driven by the smooth muscle cells (SMCs) in the media, a detailed understanding of the mechanical environment of the SMCs should reveal the mechanism of the adaptation. As the mechanical properties of the media are highly heterogeneous at the microscopic level, the mechanical properties of the cells should be measured directly. The tensile properties of SMCs are, thus, important to reveal the microscopic mechanical environment in vascular tissues; their tensile properties have a close correlation with the distribution and arrangement of elements of the cytoskeletal networks, such as stress fibers and microtubules. In this review, we first introduce the experimental techniques used for tensile testing and discuss the various factors affecting the tensile properties of vascular SMCs. Cytoskeletal networks are particularly important for the mechanical properties of a cell and its mechanism of mechanotransduction; thus, the mechanical properties of cytoskeletal filaments and their effects on whole-cell mechanical properties are discussed with special attention to the balance of intracellular forces among the intracellular components that determines the force applied to each element of the cytoskeletal filaments, which is the key to revealing the mechanotransduction events regulating mechanical adaptation. Lastly, we suggest future directions to connect tissue and cell mechanics and to elucidate the mechanism of mechanical adaptation, one of the key issues of cardiovascular solid biomechanics. 相似文献
3.
Alba Zuidema Wei Wang Arnoud Sonnenberg 《BioEssays : news and reviews in molecular, cellular and developmental biology》2020,42(11):2000119
Physical forces regulate numerous biological processes during development, physiology, and pathology. Forces between the external environment and intracellular actin cytoskeleton are primarily transmitted through integrin-containing focal adhesions and cadherin-containing adherens junctions. Crosstalk between these complexes is well established and modulates the mechanical landscape of the cell. However, integrins and cadherins constitute large families of adhesion receptors and form multiple complexes by interacting with different ligands, adaptor proteins, and cytoskeletal filaments. Recent findings indicate that integrin-containing hemidesmosomes oppose force transduction and traction force generation by focal adhesions. The cytolinker plectin mediates this crosstalk by coupling intermediate filaments to the actin cytoskeleton. Similarly, cadherins in desmosomes might modulate force generation by adherens junctions. Moreover, mechanotransduction can be influenced by podosomes, clathrin lattices, and tetraspanin-enriched microdomains. This review discusses mechanotransduction by multiple integrin- and cadherin-based cell adhesion complexes, which together with the associated cytoskeleton form an integrated network that allows cells to sense, process, and respond to their physical environment. 相似文献
4.
Vascular disease is a common cause of death within the United States. Herein, we present a method to examine the contribution of flow dynamics towards vascular disease pathologies. Unhealthy arteries often present with wall stiffening, scarring, or partial stenosis which may all affect fluid flow rates, and the magnitude of pulsatile flow, or pulsatility index. Replication of various flow conditions is the result of tuning a flow pressure damping chamber downstream of a blood pump. Introduction of air within a closed flow system allows for a compressible medium to absorb pulsatile pressure from the pump, and therefore vary the pulsatility index. The method described herein is simply reproduced, with highly controllable input, and easily measurable results. Some limitations are recreation of the complex physiological pulse waveform, which is only approximated by the system. Endothelial cells, smooth muscle cells, and fibroblasts are affected by the blood flow through the artery. The dynamic component of blood flow is determined by the cardiac output and arterial wall compliance. Vascular cell mechano-transduction of flow dynamics may trigger cytokine release and cross-talk between cell types within the artery. Co-culture of vascular cells is a more accurate picture reflecting cell-cell interaction on the blood vessel wall and vascular response to mechanical signaling. Contribution of flow dynamics, including the cell response to the dynamic and mean (or steady) components of flow, is therefore an important metric in determining disease pathology and treatment efficacy. Through introducing an in vitro co-culture model and pressure damping downstream of blood pump which produces simulated cardiac output, various arterial disease pathologies may be investigated. 相似文献
5.
6.
Mohamed JS Hajira A Li Z Paulin D Boriek AM 《The Journal of biological chemistry》2011,286(50):43394-43404
Bronchial biopsies of asthmatic patients show a negative correlation desmin expression in airway smooth muscle cell (ASMC) and airway hyperresponsiveness. We previously showed that desmin is an intracellular load-bearing protein, which influences airway compliance, lung recoil, and airway contractile responsiveness (Shardonofsky, F. R., Capetanaki, Y., and Boriek, A. M. (2006) Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L890-L896). These results suggest that desmin may play an important role in ASMC homeostasis. Here, we report that ASMCs of desmin null mice (ASMCs(Des-/-)) show hypertrophy and up-regulation microRNA-26a (miR-26a). Knockdown of miR-26a in ASMCs(Des-/-) inhibits hypertrophy, whereas enforced expression of miR-26a in ASMCs(Des+/+) induces hypertrophy. We identify that Egr1 (early growth responsive protein-1) activates miR-26a promoter via enhanced phosphorylation of Erk1/2 in ASMCs(Des-/-). We show glycogen synthase kinase-3β (GSK-3β) as a target gene of miR-26a. Moreover, induction of ASMCs(Des-/-) hypertrophy by the Erk-1/2/Egr-1/miR-26a/GSK-3β pathway is consistent in human recombinant ASMCs, which stably suppresses 90% endogenous desmin expression. Overall, our data demonstrate a novel role for desmin as an anti-hypertrophic protein necessary for ASMC homeostasis and identifies desmin as a novel regulator of microRNA. 相似文献
7.
Vascular functions are regulated not only by chemical mediators, such as hormones, cytokines, and neurotransmitters, but by
mechanical hemodynamic forces generated by blood flow and blood pressure. The mechanical force-mediated regulation is based
on the ability of vascular cells, including endothelial cells and smooth muscle cells, to recognize fluid mechanical forces,
i.e., the shear stress produced by flowing blood and the cyclic strain generated by blood pressure, and to transmit the signals
into the cell interior, where they trigger cell responses that involve changes in cell morphology, cell function, and gene
expression. Recent studies have revealed that immature cells, such as endothelial progenitor cells (EPCs) and embryonic stem
(ES) cells, as well as adult vascular cells, respond to fluid mechanical forces. Shear stress and cyclic strain promote the
proliferation and differentiation of EPCs and ES cells into vascular cells and enhance their ability to form new vessels.
Even more recently, attempts have been made to apply fluid mechanical forces to EPCs and ES cells cultured on polymer tubes
and develop tissue-engineered blood vessel grafts that have a structure and function similar to that of blood vessels in vivo.
This review summarizes the current state of knowledge concerning the mechanobiological responses of stem/progenitor cells
and its potential applications to tissue engineering. 相似文献
8.
Hemodynamic forces affect endothelial cell morphology and function. In particular, circumferential cyclic stretch of blood
vessels, due to pressure changes during the cardiac cycle, is known to affect the endothelial cell shape, mediating the alignment
of the cells in the direction perpendicular to stretch. This change in cell shape proceeds a drastic reorganization at the
internal level. The cellular scaffolding, mainly composed of actin filaments, reorganize in the direction which later becomes
the cell’s long axis. How this external mechanical stimulus is ’sensed’ and transduced into the cell is still unknown. Here,
we develop a mathematical model depicting the dynamics of actin filaments, and the influence of the cyclic stretch of the
substratum based on the experimental evidence that external stimuli may be transduced inside the cell via transmembrane proteins
which are coupled with actin filaments on the cytoplasmic side. Based on this view, we investigate two approaches describing
the formulation of the transduction mechanisms involving the coupling between filaments and the membrane proteins. As a result,
we find that the mechanical stimulus could cause the experimentally observed reorganization of the entire cytoskeleton simply
by altering the dynamics of the filaments connected with the integral membrane proteins, as described in our model. Comparison
of our results with previous studies of cytoskeletal dynamics reveals that the cytoskeleton, which, in the absence of the
effect of stretch would maintain its isotropic distribution, slowly aligns with the precise direction set by the external
stimulus. It is found that even a feeble stimulus, coupled with a strong internal dynamics, is sufficient to align actin filaments
perpendicular to the direction of stretch. 相似文献
9.
Hongyu Wang Huijuan Yao Bing Yi Kyosuke Kazama Yan Liu Deepak Deshpande Jian Zhang Jianxin Sun 《Journal of cellular physiology》2019,234(1):369-381
Abnormal airway smooth muscle cell (ASMC) proliferation and migration contribute significantly to increased ASM mass associated with asthma. MicroRNA (miR)-638 is a primate-specific miRNA that plays important roles in development, DNA damage repair, hematopoiesis, and tumorigenesis. Although it is highly expressed in ASMCs, its function in ASM remodeling remains unknown. In the current study, we found that in response to various mitogenic stimuli, including platelet-derived growth factor-two B chains (PDGF-BB), transforming growth factor β1, and fetal bovine serum, the expression of miR-638, as determined by quantitative real-time polymerase chain reaction (qRT-PCR), was significantly downregulated in the proliferative human ASMCs. Both gain- and loss-of-function studies were performed to study the role of miR-638 in ASMC proliferation and migration. We found that adenovirus-mediated miR-638 overexpression markedly inhibits ASMC proliferation and migration, while ablation of miR-638 by anti-miR-638 markedly increases cell proliferation and migration, as determined by WST-8 proliferation and scratch wound assays. Dual-luciferase reporter assay, qRT-PCR, and immunoblot analysis were used to investigate the effects of miR-638 on the expression of the downstream target genes in ASMCs. Our results demonstrated that miR-638 overexpression significantly reduced the expression of downstream target cyclin D1 and NOR1, both of which have been shown to be essential for cell proliferation and migration. Together, our study provides the first in vitro evidence highlighting the antiproliferative and antimigratory roles of miR-638 in human ASMC remodeling and suggests that targeted overexpression of miR-638 in ASMCs may provide a novel therapeutic strategy for preventing ASM hyperplasia associated with asthma. 相似文献
10.
Maja Matis 《BioEssays : news and reviews in molecular, cellular and developmental biology》2020,42(5):1900244
During morphogenesis, tissues undergo extensive remodeling to get their final shape. Such precise sculpting requires the application of forces generated within cells by the cytoskeleton and transmission of these forces through adhesion molecules within and between neighboring cells. Within individual cells, microtubules together with actomyosin filaments and intermediate filaments form the composite cytoskeleton that controls cell mechanics during tissue rearrangements. While studies have established the importance of actin-based mechanical forces that are coupled via intercellular junctions, relatively little is known about the contribution of other cytoskeletal components such as microtubules to cell mechanics during morphogenesis. In this review the focus is on recent findings, highlighting the direct mechanical role of microtubules beyond its well-established role in trafficking and signaling during tissue formation. 相似文献
11.
Cellular mechanics and gene expression in blood vessels 总被引:12,自引:0,他引:12
12.
M Holley 《BioEssays : news and reviews in molecular, cellular and developmental biology》1991,13(3):115-120
Mammalian outer hair cells generate mechanical forces at acoustic frequencies and can thus amplify the sound stimulus within the inner ear. The mechanism of force generation depends upon the plasma membrane potential but not upon either calcium or ATP. Forces are generated in the lateral cortex along the full length of the cell. The cortex includes a two-dimensional cytoskeletal lattice composed of circumferential filaments 6-7 nm thick that are cross-linked by filaments 3-4 nm thick and 40-60 nm long. The two filament types may, respectively, be actin and some form of spectrin. The lattice reinforces the cylindrical shape of the cell and permits limited changes in length. Beneath it lie the lateral cisternae, a regular system of multi-layered membranes. Force-generation may depend upon voltage-dependent shape changes in proteins that lie either in the plasma membrane or in the cytoskeletal lattice. 相似文献
13.
Bia D Pessana F Armentano R Pérez H Graf S Zócalo Y Saldías M Perez N Alvarez O Silva W Machin D Sueta P Ferrin S Acosta M Alvarez I 《Cell and tissue banking》2006,7(3):183-194
The viscoelastic and inertial properties of the arterial wall are responsible for the arterial functional role in the cardiovascular
system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but it is controversially suspected
to affect the dynamic behaviour of these allografts. The aim of this work was to assess the cryopreservation's effects on
human arteries mechanical properties. Common carotid artery (CCA) segments harvested from donors were divided into two groups:
Fresh (n = 18), tested for 24–48 h after harvesting, and Cryopreserved (n = 18) for an average time of 30 days in gas-nitrogen phase, and finally defrosted. Each segment was tested in a circulation
mock, and its pressure and diameter were registered at similar pump frequency, pulse and mean pressure levels, including those
of normotensive and hipertensive conditions. A compliance transfer function (diameter/pressure) derived from a mathematical
adaptive modelling was designed for the on line assessment of the arterial wall dynamics and its frequency response. Assessment
of arterial wall dynamics was made by measuring its viscous (η), inertial (M) and elastic (E) properties, and creep and stress relaxation time constant (τC and τSR, respectively). The frequency response characterization allowed to evaluate the arterial wall filter or buffer function.
Results showed that non-significant differences exist between wall dynamics and buffer function of fresh and cryopreserved
segments of human CCA. In conclusion, our cryopreservation method maintains arterial wall functional properties, close to
their fresh values. 相似文献
14.
Halwani R Al-Abri J Beland M Al-Jahdali H Halayko AJ Lee TH Al-Muhsen S Hamid Q 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(7):4156-4163
The increase in airway smooth muscle (ASM) mass is a major structural change in asthma. This increase has been attributed to ASM cell (ASMC) hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced, suggesting migration of smooth muscle cells toward the epithelium. Recent studies have suggested a role of chemokines in ASMC migration toward the epithelium; however, chemokines have other biological effects. The objective of the current study is to test the hypothesis that chemokines (eotaxin, RANTES, IL-8, and MIP-1α) can directly influence ASMC mass by increasing the rate of proliferation or enhancing the survival of these cells. Human ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8, or MIP-1α. To test for proliferation, matched control and stimulated ASMC were pulsed with [(3)H]thymidine, or ASMCs were stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V staining and flow cytometry. Expression of phosphorylated p42/p44 and MAPKs was assessed by Western blot. In a concentration-dependent manner, chemokines including eotaxin, RANTES, IL-8, and MIP-1α increased ASMC's [(3)H]thymidine incorporation and DNA synthesis. IL-8, eotaxin, and MIP-1α decreased the rate of apoptosis of ASMCs compared with the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. Moreover, inhibition of p42/p44 MAPK phosphorylation reduced the level of chemokine-induced ASM proliferation. We conclude that chemokines might contribute to airway remodeling seen in asthma by enhancing the number and survival of ASMCs. 相似文献
15.
Model for the alignment of actin filaments in endothelial cells subjected to fluid shear stress 总被引:3,自引:0,他引:3
A. Suciu G. Civelekoglu Y. Tardy J. -J. Meister 《Bulletin of mathematical biology》1997,59(6):1029-1046
Cultured vascular endothelial cells undergo significant morphological changes when subjected to sustained fluid shear stress.
The cells elongate and align in the direction of applied flow. Accompanying this shape change is a reorganization at the intracellular
level. The cytoskeletal actin filaments reorient in the direction of the cells' long axis. How this external stimulus is transmitted
to the endothelial cytoskeleton still remains unclear. In this article. we present a theoretical model accounting for the
cytoskeletal reorganization under the influence of fluid shear stress. We develop a system of integro-partial-differential
equations describing the dynamics of actin filaments, the actin-binding proteins, and the drift of transmembrane proteins
due to the fluid shear forces applied on the plasma membrane. Numerical simulations of the equations show that under certain
conditions, initially randomly oriented cytoskeletal actin filaments reorient in structures parallel to the externally applied
fluid shear forces. Thus, the model suggests a mechanism by which shear forces acting on the cell membrane can be transmitted
to the entire cytoskeleton via molecular interactions alone. 相似文献
16.
When grafted into an arterial environment in vivo, veins remodel in response to the new mechanical environment, thereby changing their mechanical properties and potentially impacting their patency as bypass grafts. Porcine saphenous veins were subjected for one week to four different ex vivo hemodynamic environments in which pressure and shear stress were varied independently, as well as an environment that mimicked that of an arterial bypass graft. After one week of ex vivo culture, the mechanical properties of intact saphenous veins were evaluated to relate specific aspects of the mechanical environment to vein remodeling and corresponding changes in mechanics. The compliance of all cultured veins tended to be less than that of fresh veins; however, this trend was more due to changes in medial and luminal areas than changes in the intrinsic properties of the vein wall. A combination of medial hypertrophy and eutrophic remodeling leads to significantly smaller (p<0.05) wall stresses measured in all cultured veins except those subjected to bypass graft conditions relative to stresses measured in fresh veins at corresponding pressures. Our results suggest that the mechanical environment effects changes in vessel size, as well as the nature of the remodeling, which contribute to altering vein mechanical properties. 相似文献
17.
Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readily explained by present paradigms of cytoskeletal and cross-bridge mechanics. There is increasing evidence that contractile activation of the smooth muscle cell involves an array of cytoskeletal processes that extend beyond cross-bridge cycling and the sliding of thick and thin filaments. We review here the evidence suggesting that the biophysical and mechanical properties of the smooth muscle cell reflect the integrated interactions of an array of highly dynamic cytoskeletal processes that both react to and transform the dynamics of cross-bridge interactions over the course of the contraction cycle. The activation of the smooth muscle cell is proposed to trigger dynamic remodeling of the actin filament lattice within cellular microdomains in response to local mechanical and pharmacological events, enabling the cell to adapt to its external environment. As the contraction progresses, the cytoskeletal lattice stabilizes, solidifies, and forms a rigid structure well suited for transmission of tension generated by the interaction of myosin and actin. The integrated molecular transitions that occur within the contractile cycle are interpreted in the context of microscale agitation mechanisms and resulting remodeling events within the intracellular microenvironment. Such an interpretation suggests that the cytoskeleton may behave as a glassy substance whose mechanical function is governed by an effective temperature. 相似文献
18.
Pressure transients resulting from square-wave changes in abdominal aortic blood flow rate were used to derive effective arterial compliance and peripheral resistance of the hind-limb circulation of anaesthetized rabbits. The model for deriving these parameters proved applicable if step changes in flow were kept less than 35% of mean flow. Under resting conditions, the effective hind-limb arterial compliance of normal rabbits averaged 3.46 X 10(-3) mL/mmHg (1 mmHg = 133.322 Pa). Hind-limb arterial compliance decreased with increasing pressure at low arterial pressures, but unlike compliance of isolated arterial segments, compliance did not vary at and above normal resting pressures. Baroreflex destimulation (bilateral carotid artery occlusion) caused an increase in effective hind-limb vascular resistance at 48.4% and a decrease of arterial compliance of 50.7%, so that the constant for flow-induced arterial pressure changes (resistance times compliance) was largely unchanged. Similarly, the arterial time constant for rabbits with chronic hypertension was similar to that for controls because threefold increases in hind-limb vascular resistance were offset by decreases in compliance. Reflex-induced decreases in arterial compliance are probably mediated by sympathetic nerves, whereas decreases associated with hypertension are related to wall hypertrophy in conjunction with increased vasomotor tone. Arterial compliance decreased with increasing pressure in hypertensive animals, but this effect was less pronounced than in normotensive rabbits. 相似文献
19.
Cellular growth and movement require both the control of direction and the physical capacity to generate forces. In animal
cells directional control and growth forces are generated by the polymerization of and traction between the elements of the
cytoskeleton. Whether actual forces generated by the cytoskeleton play a role in plant cell growth is largely unknown as the
interplay between turgor and cell wall is considered to be the predominant structural feature in plant cell morphogenesis.
We investigated the mechano-structural role of the cytoskeleton in the invasive growth of pollen tubes. These cells elongate
rapidly by tip growth and have the ability to penetrate the stigmatic and stylar tissues in order to drill their way to the
ovule. We used agents interfering with cytoskeletal functioning, latrunculin B and oryzalin, in combination with mechanical
in vitro assays. While microtubule degradation had no significant effect on the pollen tubes’ capacity to invade a mechanical
obstacle, latrunculin B decreased the pollen tubes’ ability to elongate in stiffened growth medium and to penetrate an obstacle.
On the other hand, the ability to maintain a certain growth direction in vitro was affected by the degradation of microtubules
but not actin filaments. To find out whether both cytoskeletal elements share functions or interact we used both drugs in
combination resulting in a dramatic synergistic response. Fluorescent labeling revealed that the integrity of the microtubule
cytoskeleton depends on the presence of actin filaments. In contrast, actin filaments seemed independent of the configuration
of microtubules. 相似文献
20.
Integrins and extracellular matrix in mechanotransduction 总被引:1,自引:0,他引:1
Schwartz MA 《Cold Spring Harbor perspectives in biology》2010,2(12):a005066
Integrins bind extracellular matrix fibrils and associate with intracellular actin filaments through a variety of cytoskeletal linker proteins to mechanically connect intracellular and extracellular structures. Each component of the linkage from the cytoskeleton through the integrin-mediated adhesions to the extracellular matrix therefore transmits forces that may derive from both intracellular, myosin-generated contractile forces and forces from outside the cell. These forces activate a wide range of signaling pathways and genetic programs to control cell survival, fate, and behavior. Additionally, cells sense the physical properties of their surrounding environment through forces exerted on integrin-mediated adhesions. This article first summarizes current knowledge about regulation of cell function by mechanical forces acting through integrin-mediated adhesions and then discusses models for mechanotransduction and sensing of environmental forces. 相似文献