Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

2007 ◽  
Vol 292 (3) ◽  
pp. H1209-H1224 ◽  
Author(s):  
Shu Chien
Keyword(s):  
Shear Stress ◽  
Complex Geometry ◽  
Vascular Endothelial Cells ◽  
The Body ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Molecular Signaling ◽  
Branch Points ◽  
Arterial Tree ◽  
The Face

Vascular endothelial cells (ECs) play significant roles in regulating circulatory functions. Mechanical stimuli, including the stretch and shear stress resulting from circulatory pressure and flow, modulate EC functions by activating mechanosensors, signaling pathways, and gene and protein expressions. Mechanical forces with a clear direction (e.g., the pulsatile shear stress and the uniaxial circumferential stretch existing in the straight part of the arterial tree) cause only transient molecular signaling of pro-inflammatory and proliferative pathways, which become downregulated when such directed mechanical forces are sustained. In contrast, mechanical forces without a definitive direction (e.g., disturbed flow and relatively undirected stretch seen at branch points and other regions of complex geometry) cause sustained molecular signaling of pro-inflammatory and proliferative pathways. The EC responses to directed mechanical stimuli involve the remodeling of EC structure to minimize alterations in intracellular stress/strain and elicit adaptive changes in EC signaling in the face of sustained stimuli; these cellular events constitute a feedback control mechanism to maintain vascular homeostasis and are atheroprotective. Such a feedback mechanism does not operate effectively in regions of complex geometry, where the mechanical stimuli do not have clear directions, thus placing these areas at risk for atherogenesis. The mechanotransduction-induced EC adaptive processes in the straight part of the aorta represent a case of the “Wisdom of the Cell,” as a part of the more general concept of the “Wisdom of the Body” promulgated by Cannon, to maintain cellular homeostasis in the face of external perturbations.

Role of Mechanical Forces in Endothelial Homeostasis

2008 ◽  
Author(s):  
Shu Chien
Keyword(s):  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Mechanical Strain ◽  
Forward Direction ◽  
Mechanical Forces ◽  
Branch Points ◽  
Laminar Shear Stress ◽  
Complex Flow ◽  
Preferred Direction ◽  
Transient Activation

Shear stress and stretch can modulate functions of vascular endothelial cells (ECs) by activating mechano-sensors, signaling pathways, and gene/protein expressions. Sustained shear stress with a forward direction causes only a transient activation of atherogenic genes, followed by down-regulation. In ECs exposed to complex flow with little forward direction, activation of these atherogenic genes is sustained, and cell turnover is accelerated. Cyclic uniaxial stretch causes orientation of actin stress fibers perpendicular to stretch direction, and this causes a decrease of intracellular stress, transient JNK activation, and protection of ECs against apoptosis. Cyclic biaxial stretch without a preferred direction has opposite effects. In the straight arteries, laminar shear stress with a forward direction and uniaxial strain with a circumferential direction have anti-atherogenic effects. At branch points, the complex shear flow and mechanical strain with little net direction are atherogenic. The direction of mechanical forces has important effects on ECs in health and disease.

Modulation of membrane traffic by mechanical stimuli

2002 ◽  
Vol 282 (2) ◽  
pp. F179-F190 ◽  
Author(s):  
Gerard Apodaca
Keyword(s):  
Shear Stress ◽  
Plasma Membrane ◽  
Tyrosine Kinases ◽  
Membrane Traffic ◽  
Cell Types ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Membrane Tension ◽  
External Stimuli ◽  
Stretch Activated Channels

All cells experience and respond to mechanical stimuli, such as changes in plasma membrane tension, shear stress, hydrostatic pressure, and compression. This review is an examination of the changes in membrane traffic that occur in response to mechanical forces. The plasma membrane has an associated tension that modulates both exocytosis and endocytosis. As membrane tension increases, exocytosis is stimulated, which acts to decrease membrane tension. In contrast, increased membrane tension slows endocytosis, whereas decreased tension stimulates internalization. In most cases, secretion is stimulated by external mechanical stimuli. However, in some cells mechanical forces block secretion. External stimuli also enhance membrane and fluid endocytosis in several cell types. Transduction of mechanical stimuli into changes in exocytosis/endocytosis may involve the cytoskeleton, stretch-activated channels, integrins, phospholipases, tyrosine kinases, and cAMP.

scholarly journals In Vitro Measurements of Cellular Forces and their Importance in the Lung—From the Sub- to the Multicellular Scale

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 691
Author(s):  
Peter Kolb ◽  
Annika Schundner ◽  
Manfred Frick ◽  
Kay-E. Gottschalk
Keyword(s):  
Mechanical Properties ◽  
Measurement Techniques ◽  
Short Review ◽  
Cellular Level ◽  
The Body ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Length Scales ◽  
Cellular Forces

Throughout life, the body is subjected to various mechanical forces on the organ, tissue, and cellular level. Mechanical stimuli are essential for organ development and function. One organ whose function depends on the tightly connected interplay between mechanical cell properties, biochemical signaling, and external forces is the lung. However, altered mechanical properties or excessive mechanical forces can also drive the onset and progression of severe pulmonary diseases. Characterizing the mechanical properties and forces that affect cell and tissue function is therefore necessary for understanding physiological and pathophysiological mechanisms. In recent years, multiple methods have been developed for cellular force measurements at multiple length scales, from subcellular forces to measuring the collective behavior of heterogeneous cellular networks. In this short review, we give a brief overview of the mechanical forces at play on the cellular level in the lung. We then focus on the technological aspects of measuring cellular forces at many length scales. We describe tools with a subcellular resolution and elaborate measurement techniques for collective multicellular units. Many of the technologies described are by no means restricted to lung research and have already been applied successfully to cells from various other tissues. However, integrating the knowledge gained from these multi-scale measurements in a unifying framework is still a major future challenge.

An Ultrastructural Study of Pericytes

1968 ◽  
Vol 26 ◽  
pp. 66-67
Author(s):  
T. M. Murad ◽  
E. von Haam
Keyword(s):  
Plasma Membrane ◽  
Endothelial Cell ◽  
Basement Membrane ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Myoepithelial Cells ◽  
Capillary Blood ◽  
The Body ◽  
Capillary Blood Vessel ◽  
Outer Plasma Membrane

Pericytes are vascular satellites present around capillary blood vessels and small venules. They have been observed in almost every tissue of the body and are thought to be related to vascular smooth muscle cells. Morphologically pericytes have great similarity to vascular endothelial cells and also slightly resemble myoepithelial cells.The present study describes the ultrastructural morphology of pericytes in normal breast tissue and in benign tumor of the breast. The study showed that pericytes are ovoid or elongated cells separated from the endothelial cell of the capillary blood vessel by the basement membrane of endothelial cell. The nuclei of pericytes are often very distinctive. Although some are round, oval, or elongated, others show marked irregularity and infolding of the nuclear membrane. The cytoplasm shows mono-or bipolar extension in which the cytoplasmic organelles are located (Fig. 1). These cytoplasmic extensions embrace the capillary blood vessel incompletely. The plasma membrane exhibits multiple areas of focal condensation called hemidesmosomes (Fig. 2, arrow). A variable number of pinocytotic vesicles are frequently seen lining the outer plasma membrane. Normally pericytes are surrounded by a basement membrane which is found more consistently on the outer plasma membrane separating the pericytes from the stromal connective tissue.

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.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

scholarly journals Keloidal pathophysiology: Current notions

2021 ◽  
Vol 7 ◽  
pp. 205951312098032
Author(s):  
Chenyu Huang ◽  
Rei Ogawa
Keyword(s):  
Web Of Science ◽  
English Literature ◽  
The Body ◽  
Mechanical Forces ◽  
Healthy Skin ◽  
Level Of Evidence ◽  
Extracellular Matrix Components ◽  
Keloid Formation ◽  
Mechanical Factors ◽  
Pathological Scar

Introduction: Keloids are pathological scars that are notorious for their chronic and relentless invasion into adjacent healthy skin, with commonly seen post-therapeutic recurrence after monotherapies. Methods: An English literature review on keloid pathophysiology was performed by searching the PubMed, Embase and Web of Science databases, to find out the up-to-date relevant articles. The level of evidence was evaluated based on the included studies with the highest level of evidence first. Results: Keloid morphology, signs, symptoms and the histopathological changes that occur in the local cells and extracellular matrix components are described. The theories on the pathophysiology of keloidogenesis that have been proposed to date are also covered; these include endocrinological, nutritional, vascular, and autoimmunological factors. In addition, we describe the local mechanical forces (and the mechanosignalling pathways by which these forces shape keloid cell activities) that promote keloid formation and determine the direction of invasion of keloids and the body sites that are prone to them. Conclusion: A better understanding of this pathological entity, particularly its mechanobiology, will aid the development of new diagnostic and therapeutic strategies for use in the clinic to prevent, reduce or even reverse the growth of this pathological scar. Lay Summary Keloids are skin scars that are famous for their chronic invasion into healthy skin, with commonly seen recurrence after surgeries. Cells such as lymphocytes, macrophages, mast cells and endothelial cells are involved in keloid growth. Particularly, endocrinological, nutritional, vascular, autoimmunological and mechanical factors actively take part in keloid progression.

scholarly journals Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 765
Author(s):  
Qianbin Zhao ◽  
Tim Cole ◽  
Yuxin Zhang ◽  
Shi-Yang Tang
Keyword(s):  
Cell Culture ◽  
Shear Stress ◽  
Cultured Cells ◽  
Mechanical Strain ◽  
3D Cell Culture ◽  
Small Scale ◽  
Mechanical Stimuli ◽  
Human Organ ◽  
Organ On A Chip

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.

Circadian tuning of motivation. A little organ of yesterday?

1995 ◽  
Vol 7 (2) ◽  
pp. 21-23 ◽  
Author(s):  
S. Daan
Keyword(s):  
Internal State ◽  
External Environment ◽  
Animal Behaviour ◽  
The Body ◽  
Biological Clocks ◽  
Motivational Systems ◽  
Regulatory Principle ◽  
The Face ◽  
Temporal Organisation ◽  
The Ideal

The analysis of motivational systems underlying temporal organisation in animal behaviour has relied primarily on two conceptual functional frameworks: Homeostasis and biological clocks. Homeostasis is one of the most general and influential concepts in physiology. Walter Cannon introduced homeostasis as a universal regulatory principle which animals employ to maintain constancy of their ‘internal milieu’ in the face of challenges and perturbations from the external environment. Cannon spoke of “The Wisdom of the Body”, the collective of responses designed to defend the ideal internal state against those perturbations.

Sign in / Sign up

Export Citation Format

Share Document