Influence of power-law rheology on cell injury during microbubble flows

Dailey, Hannah L.; Ghadiali, Samir N.

doi:10.1007/s10237-009-0175-0

Cited by 22 publications

(26 citation statements)

References 40 publications

(103 reference statements)

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“…5B, A549 cells exhibit a complex rheology where the storage modulus follows a weak power law function of frequency with a power law exponent, ␣. Previous computational studies (13) predict that increases in ␣ result in a more fluidlike cell, and that this fluidization results in less plasma membrane rupture during airway reopening. Consistent with these computational predictions, Yalcin et al (47) demonstrated that depolymerizating the actin cytoskeleton leads to a large increase in ␣ and lower cell necrosis during cyclic airway reopening.…”

Section: Discussionmentioning

confidence: 99%

“…Under these conditions, the closure and reopening of fluid-filled airways generates interfacial and microbubble flows that can significantly damage the lung epithelium. Specifically, several investigators have used computational (13,14,23,25,29) and in vitro experimental (3,30,47,48) techniques to demonstrate that this interfacial flow generates complex mechanical forces that cause cell necrosis/plasma membrane disruption and detachment of cells from their substrate. In addition, mechanical forces associate with atelectrauma can also activate inflammatory signaling pathways (27,28).…”

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confidence: 99%

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Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows

Higuita‐Castro

Mihai

Hansford

et al. 2014

Journal of Applied Physiology

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Higuita-Castro N, Mihai C, Hansford DJ, Ghadiali SN. Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows. J Appl Physiol 117: 1231-1242, 2014. First published September 11, 2014 doi:10.1152/japplphysiol.00752.2013.-Interfacial flows during cyclic airway reopening are an important source of ventilator-induced lung injury. However, it is not known how changes in airway wall compliance influence cell injury during airway reopening. We used an in vitro model of airway reopening in a compliant microchannel to investigate how airway wall stiffness influences epithelial cell injury. Epithelial cells were grown on gel substrates with different rigidities, and cellular responses to substrate stiffness were evaluated in terms of metabolic activity, mechanics, morphology, and adhesion. Repeated microbubble propagations were used to simulate cyclic airway reopening, and cell injury and detachment were quantified via live/dead staining. Although cells cultured on softer gels exhibited a reduced elastic modulus, these cells experienced less plasma membrane rupture/necrosis. Cells on rigid gels exhibited a minor, but statistically significant, increase in the power law exponent and also exhibited a significantly larger height-to-length aspect ratio. Previous studies indicate that this change in morphology amplifies interfacial stresses and, therefore, correlates with the increased necrosis observed during airway reopening. Although cells cultured on stiff substrates exhibited more plasma membrane rupture, these cells experienced significantly less detachment and monolayer disruption during airway reopening. Western blotting and immunofluorescence indicate that this protection from detachment and monolayer disruption correlates with increased focal adhesion kinase and phosphorylated paxillin expression. Therefore, changes in cell morphology and focal adhesion structure may govern injury responses during compliant airway reopening. In addition, these results indicate that changes in airway compliance, as occurs during fibrosis or emphysema, may significantly influence cell injury during mechanical ventilation.ventilation-induced lung injury; airway compliance; airway reopening; cell mechanics; and cell injury THE ACUTE RESPIRATORY DISTRESS syndrome (ARDS) is a lifethreatening condition that involves disruption of the alveolarcapillary barrier and impaired gas exchange (46).1 Although mechanical ventilation of ARDS patients can restore normal oxygenation, these ventilators may also cause significant cellular injury and trigger proinflammatory signaling cascades (26, 31) in a process known as ventilator-induced lung injury (VILI). One form of VILI, known as volutrauma, involves the overdistension and cyclic stretching of lung tissue, which causes epithelial cell necrosis (43), disruption of the alveolarcapillary barrier (7), and inflammatory signaling (44). Presently, protective ventilation strategies, such as low tidal volumes, are the standard of care and seek to minimize volutrau...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows

Higuita‐Castro

Mihai

Hansford

et al. 2014

Journal of Applied Physiology

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“…In a separate study, these authors also demonstrated that changes in the cell's biophysical properties can be used to prevent cellular necrosis and detachment during microbubble flows [20]. In support of this concept, Dailey and Ghadiali [21,22] have recently used imaged-based computational techniques to investigate how changes in cellular mechanics and morphology may be used to prevent cell injury and deformation. Naire and Jensen [23] also used theoretical models to show that the elastic modulus of the epithelial layer plays a key role in deter mining cell deformation during microbubble flows.…”

Section: Introductionmentioning

confidence: 94%

Computational Analysis of Microbubble Flows in Bifurcating Airways: Role of Gravity, Inertia, and Surface Tension

Chen

Zielinski

Ghadiali

2014

Journal of Biomechanical Engineering

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Although mechanical ventilation is a life-saving therapy for patients with severe lung disorders, the microbubble flows generated during ventilation generate hydrodynamic stresses, including pressure and shear stress gradients, which damage the pulmonary epithelium. In this study, we used computational fluid dynamics to investigate how gravity, inertia, and surface tension influence both microbubble flow patterns in bifurcating airways and the magnitude/distribution of hydrodynamic stresses on the airway wall. Direct interface tracking and finite element techniques were used to simulate bubble propagation in a two-dimensional (2D) liquid-filled bifurcating airway. Computational solutions of the full incompressible Navier-Stokes equation were used to investigate how inertia, gravity, and surface tension forces as characterized by the Reynolds (Re), Bond (Bo), and Capillary (Ca) numbers influence pressure and shear stress gradients at the airway wall. Gravity had a significant impact on flow patterns and hydrodynamic stress magnitudes where Bo > 1 led to dramatic changes in bubble shape and increased pressure and shear stress gradients in the upper daughter airway. Interestingly, increased pressure gradients near the bifurcation point (i.e., carina) were only elevated during asymmetric bubble splitting. Although changes in pressure gradient magnitudes were generally more sensitive to Ca, under large Re conditions, both Re and Ca significantly altered the pressure gradient magnitude. We conclude that inertia, gravity, and surface tension can all have a significant impact on microbubble flow patterns and hydrodynamic stresses in bifurcating airways.

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“…Results showed that mechanical strain induces the upregulation of collagen III and IV, as well as MMP-2 and -9 expressions by lung fibroblasts, indicating a remodeling response of the tissue in vitro. Furthermore, studies have reported that the 3D computational models can be very useful in predicting cell-ligand or cell-cell interactions as well as in modeling mechanobiological responses such as epithelial layer disruption under the influence of hydraulic stresses generated by the movement of air-liquid interface or microbubble flow (36,87).…”

Section: Tissue-engineered Lung Models In Drug Development and Discoverymentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models. bioengineered lung; computational modeling; in silico; lung models; tissue engineering LUNG DISEASES ARE THE THIRD leading cause of deaths in the United States that translate into one in six deaths. More than 400,000 Americans die of lung disease every year and around 35 million are now living with chronic lung problems (1). Therefore, there is an important need to understand as to how a new drug entity or a novel formulation may influence the anatomy, physiology, and pathogenesis of lungs and vice versa.The human lung has an approximate volume of six liters, contains about 300 million alveoli, and provides a total surface area of 100 square meters as blood-air interface, which is packed into an elastic dynamic structure responsible for gas exchange (159). The human airway wall is a connective tissue that includes smooth muscle cells (SMC), mucus glands, blood vessels, and fibroblasts surrounded by a collagen-rich extracellular matrix (ECM). Epithelial cells, responsible for the efficient oxygen and carbon dioxide transfer, are at the interface between air and the connective tissue and are attached to an underlying basement membrane. The respiratory system is the site of a variety of pulmonary diseases such as asthma, bronchitis, pneumonia, cystic fibrosis, emphysema, a...

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Influence of power-law rheology on cell injury during microbubble flows

Cited by 22 publications

References 40 publications

Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows

Influence of airway wall compliance on epithelial cell injury and adhesion during interfacial flows

Computational Analysis of Microbubble Flows in Bifurcating Airways: Role of Gravity, Inertia, and Surface Tension

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

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