Testing Different Hypotheses of Vascular Homeostasis Based on Mechanical Stress or Strain in Image-Based Models Using an Inverse Method

2011 ◽  
Author(s):  
Shahrokh Zeinali-Davarani ◽  
Seungik Baek
Keyword(s):  
Inverse Method ◽  
Arterial Wall ◽  
Vascular Tissue ◽  
Optimization Method ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Physiological Conditions ◽  
Mechanical Quantity ◽  
Mechanical Homeostasis

Various hypotheses are previously suggested to describe the tendency of vascular tissue to adapt in response to alterations in mechanical stimuli. It is still a matter of controversy which mechanical quantity governs or correlates well with the adaptation, contributing to the mechanical homeostasis. A computational tool that can distinguish between different hypotheses under various physiological conditions may help better understanding of the governing rules. Recently, an inverse optimization method has been developed to estimate the optimal spatial distributions of arterial wall thickness and material anisotropy of image-based models while satisfying a homeostatic condition assumed [1]. The same numerical method can be utilized to investigate the consequent optimal structures resulting from different hypotheses for the mechanical homeostasis. We consider three hypotheses for a homeostatic state based on intramural stress or cyclic stretch and examine their effects on the optimized distributions of thickness and anisotropy. The results show the capability of the presented method in discriminating different hypotheses of vascular homeostasis with image-based models, the validity of which requires more experimental data.

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.

scholarly journals Study of the Hemodynamics Effects of an Isolated Systolic Hypertension (ISH) Condition on Cerebral Aneurysms Models, Using FSI Simulations

2021 ◽  
Vol 11 (6) ◽  
pp. 2595
Author(s):  
José Barahona ◽  
Alvaro Valencia ◽  
María Torres
Keyword(s):  
Systolic Hypertension ◽  
Arterial Wall ◽  
Abrupt Change ◽  
Cerebral Aneurysms ◽  
Rupture Risk ◽  
Pressure Condition ◽  
Isolated Systolic Hypertension ◽  
Hemodynamic Changes ◽  
Physiological Conditions ◽  
Relative Residence Time

Hemodynamics is recognized as a relevant factor in the development and rupture of cerebral aneurysms, so further studies related to different physiological conditions in human represent an advance in understanding the pathology and rupture risk. In this paper, Fluid-structure interaction simulations (FSI) were carried out in six models of cerebral aneurysms, in order to study the hemodynamics effects of an isolated systolic hypertension (ISH) condition and compare it to a normal or normotensive pressure condition and a higher hypertension condition. Interestingly, the ISH condition showed, in general, the greatest hemodynamics changes, evidenced in the Time-Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) parameters, with respect to a normal condition. These results could imply that a not high-pressure condition (ISH), characterized with a different shape and an abrupt change in its diastolic and systolic range may present more adverse hemodynamic changes compared to a higher-pressure condition (such as a hypertensive condition) and therefore have a greater incidence on the arterial wall remodeling and rupture risk.

STRETCHABLE Lab-on-Chip Device With Impedance Spectroscopy Capability for Mammalian Cell Studies

2016 ◽  
Author(s):  
Xudong Zhang ◽  
Anis Nurashikin Nordin ◽  
Fang Li ◽  
Ioana Voiculescu
Keyword(s):  
Impedance Spectroscopy ◽  
Mammalian Cells ◽  
Dynamic Environment ◽  
Cyclic Strain ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Aortic Endothelial Cells ◽  
Lab On Chip

This paper presents the fabrication and testing of electric cell-substrate impedance spectroscopy (ECIS) electrodes on a stretchable membrane. This is the first time when ECIS electrodes were fabricated on a stretchable substrate and ECIS measurements on mammalian cells exposed to cyclic strain of 10% were successfully demonstrated. A chemical was used to form strong chemical bond between gold electrodes of ECIS sensor and polymer membrane, which enable the electrodes keep good conductive ability during cyclic stretch. The stretchable membrane integrated with the ECIS sensor can simulate and replicate the dynamic environment of organism and enable the analysis of the cells activity involved in cells attachment and proliferation in vitro. Bovine aortic endothelial cells (BAEC) were used to evaluate the endothelial function influenced by mechanical stimuli in this research because they undergo in vivo cyclic physiologic elongation produced by the blood circulation in the arteries.

scholarly journals Baseline Stiffness Modulates the Non-Linear Response to Stretch of the Extracellular Matrix in Pulmonary Fibrosis

2021 ◽  
Vol 22 (23) ◽  
pp. 12928
Author(s):  
Constança Júnior ◽  
Maria Narciso ◽  
Esther Marhuenda ◽  
Isaac Almendros ◽  
Ramon Farré ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Fibrosis ◽  
Strain Hardening ◽  
Mechanical Behaviour ◽  
Cyclic Stretch ◽  
In Vivo Model ◽  
Micromechanical Properties ◽  
Order Of Magnitude ◽  
Mechanical Homeostasis

Pulmonary fibrosis (PF) is a progressive disease that disrupts the mechanical homeostasis of the lung extracellular matrix (ECM). These effects are particularly relevant in the lung context, given the dynamic nature of cyclic stretch that the ECM is continuously subjected to during breathing. This work uses an in vivo model of pulmonary fibrosis to characterize the macro- and micromechanical properties of lung ECM subjected to stretch. To that aim, we have compared the micromechanical properties of fibrotic ECM in baseline and under stretch conditions, using a novel combination of Atomic Force Microscopy (AFM) and a stretchable membrane-based chip. At the macroscale, fibrotic ECM displayed strain-hardening, with a stiffness one order of magnitude higher than its healthy counterpart. Conversely, at the microscale, we found a switch in the stretch-induced mechanical behaviour of the lung ECM from strain-hardening at physiological ECM stiffnesses to strain-softening at fibrotic ECM stiffnesses. Similarly, we observed solidification of healthy ECM versus fluidization of fibrotic ECM in response to stretch. Our results suggest that the mechanical behaviour of fibrotic ECM under stretch involves a potential built-in mechanotransduction mechanism that may slow down the progression of PF by steering resident fibroblasts away from a pro-fibrotic profile.

scholarly journals Mechanical Stimuli Affect Escherichia coli Heat-Stable Enterotoxin-Cyclic GMP Signaling in a Human Enteroid Intestine-Chip Model

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Laxmi Sunuwar ◽  
Jianyi Yin ◽  
Magdalena Kasendra ◽  
Katia Karalis ◽  
James Kaper ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cell ◽  
Cyclic Gmp ◽  
Cyclic Stretch ◽  
Intestinal Bacterium ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Content Type ◽  
Heat Stable ◽  
Static Conditions

ABSTRACT Modeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells to mechanical forces normally present in the intestine, including luminal flow and serosal blood flow (shear force) or peristaltic forces. To determine the contribution of mechanical forces in the functional response of human small intestine to a virulence factor of a pathogenic intestinal bacterium, human jejunal enteroids were cultured as monolayers in microengineered fluidic-based Organ-Chips (Intestine-Chips) exposed to enterotoxigenic Escherichia coli heat-stable enterotoxin A (ST) and evaluated under conditions of static fluid, apical and basolateral flow, and flow plus repetitive stretch. Application of flow increased epithelial cell height and apical and basolateral secretion of cyclic GMP (cGMP) under baseline, unstimulated conditions. Addition of ST under flow conditions increased apical and basolateral secretion of cGMP relative to the level under static conditions but did not enhance intracellular cGMP accumulation. Cyclic stretch did not have any significant effect beyond that contributed by flow. This study demonstrates that fluid flow application initiates changes in intestinal epithelial cell characteristics relative to those of static culture conditions under both baseline conditions and with exposure to ST enterotoxin and suggests that further investigations of the application of these mechanical forces will provide insights into physiology and pathophysiology that more closely resemble intact intestine than study under static conditions.

scholarly journals Elastomeric Electrospun Scaffolds of a Biodegradable Aliphatic Copolyester Containing PEG-Like Sequences for Dynamic Culture of Human Endothelial Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1620
Author(s):  
Luca Fusaro ◽  
Chiara Gualandi ◽  
Diego Antonioli ◽  
Michelina Soccio ◽  
Anna Liguori ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Vascular Tissue ◽  
Mechanical Performance ◽  
Thrombus Formation ◽  
Cell Activity ◽  
Mechanical Tests ◽  
Cyclic Stretch ◽  
Biological Characterization ◽  
The Right

In the field of artificial prostheses for damaged vessel replacement, polymeric scaffolds showing the right combination of mechanical performance, biocompatibility, and biodegradability are still demanded. In the present work, poly(butylene-co-triethylene trans-1,4-cyclohexanedicarboxylate), a biodegradable random aliphatic copolyester, has been synthesized and electrospun in form of aligned and random fibers properly designed for vascular applications. The obtained materials were analyzed through tensile and dynamic-mechanical tests, the latter performed under conditions simulating the mechanical contraction of vascular tissue. Furthermore, the in vitro biological characterization, in terms of hemocompatibility and cytocompatibility in static and dynamic conditions, was also carried out. The mechanical properties of the investigated scaffolds fit within the range of physiological properties for medium- and small-caliber blood vessels, and the aligned scaffolds displayed a strain-stiffening behavior typical of the blood vessels. Furthermore, all the produced scaffolds showed constant storage and loss moduli in the investigated timeframe (24 h), demonstrating the stability of the scaffolds under the applied conditions of mechanical deformation. The biological characterization highlighted that the mats showed high hemocompatibility and low probability of thrombus formation; finally, the cytocompatibility tests demonstrated that cyclic stretch of electrospun fibers increased endothelial cell activity and proliferation, in particular on aligned scaffolds.

scholarly journals Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues

2021 ◽  
Vol 12 ◽  
Author(s):  
Hamza Atcha ◽  
Vijaykumar S. Meli ◽  
Chase T. Davis ◽  
Kyle T. Brumm ◽  
Sara Anis ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Inflammatory Responses ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Cd11b Expression ◽  
Static Stretch ◽  
Knock Down ◽  
Form And Function ◽  
Cytokines And Chemokines ◽  
And Function

Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While the effects of soluble cues, including cytokines and chemokines, have been widely studied, the effects of physical cues, including mechanical stimuli, in regulating macrophage form and function are less well understood. In this study, we examined the effects of static and cyclic uniaxial stretch on macrophage inflammatory and healing activation. We found that cyclic stretch altered macrophage morphology and responses to IFNγ/LPS and IL4/IL13. Interestingly, we found that both static and cyclic stretch suppressed IFNγ/LPS induced inflammation. In contrast, IL4/IL13 mediated healing responses were suppressed with cyclic but enhanced with static stretch conditions. Mechanistically, both static and cyclic stretch increased expression of the integrin CD11b (αM integrin), decreased expression of the mechanosensitive ion channel Piezo1, and knock down of either CD11b or Piezo1 through siRNA abrogated stretch-mediated changes in inflammatory responses. Moreover, we found that knock down of CD11b enhanced the expression of Piezo1, and conversely knock down of Piezo1 enhanced CD11b expression, suggesting the potential for crosstalk between integrins and ion channels. Finally, stretch-mediated differences in macrophage activation were also dependent on actin, since pharmacological inhibition of actin polymerization abrogated the changes in activation with stretch. Together, this study demonstrates that the physical environment synergizes with biochemical cues to regulate macrophage morphology and function, and suggests a role for CD11b and Piezo1 crosstalk in mechanotransduction in macrophages.

scholarly journals The actin binding protein α-adducin modulates desmosomal turnover and plasticity

2019 ◽  
Author(s):  
Matthias Hiermaier ◽  
Felix Kliewe ◽  
Camilla Schinner ◽  
Chiara Stüdle ◽  
I. Piotr Maly ◽  
...  
Keyword(s):  
Binding Protein ◽  
Intercellular Adhesion ◽  
Cyclic Stretch ◽  
Actin Binding ◽  
Mechanical Stimuli ◽  
Cortical Actin ◽  
Adhesive Properties ◽  
Actin Binding Protein ◽  
Tissue Integrity ◽  
Desmoglein 3

Intercellular adhesion is essential for tissue integrity and homeostasis. Desmosomes are especially abundant in the epidermis and the myocardium, tissues, which are under constantly changing mechanical stresses. Yet, it is largely unclear whether desmosomal adhesion can be rapidly adapted to changing demands and the mechanisms underlying desmosome turnover are only partially understood. We here show that loss of the actin-binding protein α-adducin prevented the ability of cultured keratinocytes or murine epidermis to withstand mechanical stress paralleled with reduced desmosome number. This effect was not caused by decreased levels or impaired adhesive properties of desmosomal molecules but rather by altered desmosome turnover. Mechanistically, reduced cortical actin density in α-adducin knockout keratinocytes resulted in increased mobility of the desmosomal adhesion molecule desmoglein 3 (Dsg3) and impaired interactions with E-cadherin, a crucial step in desmosome formation. Accordingly, loss of α-adducin prevented increased membrane localization of Dsg3 in response to cyclic stretch or shear stress. Our data demonstrate plasticity of desmosomal molecules in response to mechanical stimuli and unravel a mechanism how the actin cytoskeleton indirectly shapes intercellular adhesion by restricting the mobility of desmosomal molecules.

scholarly journals A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

2018 ◽  
Vol 15 (139) ◽  
pp. 20170732 ◽  
Author(s):  
Alberto Coccarelli ◽  
David Hughes Edwards ◽  
Ankush Aggarwal ◽  
Perumal Nithiarasu ◽  
Dimitris Parthimos
Keyword(s):  
Smooth Muscle ◽  
Arterial Wall ◽  
Structural Model ◽  
Vascular Tissue ◽  
Nonlinear Differential Equations ◽  
Specific Inhibitor ◽  
Intracellular Signalling ◽  
Muscle Coordination ◽  
Muscle Dynamics

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone.

scholarly journals Mechanical Stimuli Affect E. Coli Heat Stable Enterotoxin (ST)-Cyclic GMP Signaling in a Human Enteroid Intestine-Chip Diarrhea Model

2019 ◽  
Author(s):  
Laxmi Sunuwar ◽  
Jianyi Yin ◽  
Magdalena Kasendra ◽  
Katia Karalis ◽  
James Kaper ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Animal Studies ◽  
Culture Conditions ◽  
Cyclic Stretch ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
E Coli ◽  
Cell Height ◽  
Heat Stable ◽  
Static Conditions

ABSTRACTModeling host-pathogen interactions with human intestinal epithelia using enteroid monolayers on permeable supports (such as Transwells) represents an alternative to animal studies or use of colon cancer-derived cell lines. However, the static monolayer model does not expose epithelial cells to mechanical forces normally present in the intestine, including luminal flow and serosal blood flow (shear force) or peristaltic forces. To determine the contribution of mechanical forces in the functional response of human small intestine to a pathogen virulence factor, human jejunal enteroids were cultured as monolayers in microengineered fluidic-based Organ-Chips (Intestine-Chips), exposed to enterotoxigenic E. coli heat-stable enterotoxin A (ST), and evaluated under conditions of static fluid, apical and basolateral flow, and flow plus repetitive stretch. Application of flow increased epithelial cell height, transcription of the cyclic nucleotide transporting protein MRP4, and apical and basolateral secretion of cGMP under baseline, unstimulated conditions. Addition of ST under flow conditions increased apical and basolateral secretion of cGMP relative to static conditions, but did not enhance intracellular cGMP accumulation. Cyclic stretch did not have any significant effect beyond that contributed by flow. This study demonstrates that fluid flow application initiates changes in intestinal epithelial cell characteristics relative to static culture conditions under both baseline conditions and with exposure to ST enterotoxin, and suggests that further investigations of application of these mechanical forces will provide insights into physiology and pathophysiology that more closely resembles intact intestine than study under static conditions.

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