The Eustachian Tube (ET) is a collapsible tube that connects the middle ear to the nasopharynx. D... more The Eustachian Tube (ET) is a collapsible tube that connects the middle ear to the nasopharynx. Dysfunction in the ET leads to a disease called Otitis Media. Our goal is to develop and use fluid-structure interaction (FSI) models of ET opening phenomena to better understand what factors contribute to ET dysfunction in certain patients. We model the ET in COMSOL using geometric data obtained from histological specimens. Using histological data allows us to make anatomically accurate models which are then used to simulate the clinical tests performed on patients. This serves as an excellent validation tool for our COMSOL model. We have created a FSI model of a healthy ET which successfully simulated the large tissue deformations that occur during ET opening. We found that higher order basis functions were required in order to prevent element failure. We are currently extending this model to account for transient dynamics and two-way coupling.
... PATHOPHYSIOLOGY, AND PATHOGENESIS CUNEYT M. ALPER, MD, CHAIR CHARLES D. BLUESTONE, MD, CO-CHA... more ... PATHOPHYSIOLOGY, AND PATHOGENESIS CUNEYT M. ALPER, MD, CHAIR CHARLES D. BLUESTONE, MD, CO-CHAIR BERNARD ARS, MD, PHD SAMIR N. GHADIALI, PHD STEN O. HELLSTRÖM, MD, PHD J. DOUGLAS ...
A primary etiological factor underlying chronic middle ear disease is an inability to open the co... more A primary etiological factor underlying chronic middle ear disease is an inability to open the collapsible Eustachian tube (ET). However, the structure-function relationships responsible for ET dysfunction in patient populations at risk for developing otitis media (OM) are not known. In this study, three-dimensional (3D) finite element (FE) modeling techniques were used to investigate how changes in biomechanical and anatomical properties influence opening phenomena in three populations: normal adults, young children and infants with cleft palate. Histological data was used to create anatomically accurate models and FE techniques were used to simulate tissue deformation and ET opening. Lumen dilation was quantified using a computational fluid dynamic (CFD) technique and a sensitivity analysis was performed to ascertain the relative importance of the different anatomical and tissue mechanical properties. Results for adults suggest that ET function is highly sensitive to tensor veli palatini muscle (TVPM) forces and to periluminal mucosal tissue (PMT) elasticity. Young children and cleft palate subjects exhibited reduced sensitivity to TVPM forces while changes in PMT stiffness continued to have a significant impact on ET function. These results suggest that reducing PMT stiffness might be an effective way to restore ET function in these populations. Varying TVPM force vector relationships via changes in hamulus location had no effect on ET opening in young children and cleft palate subjects but did alter force transmission to the ET lumen during conditions of elevated adhesion. These models have therefore provided important new insights into the biomechanical mechanisms responsible for ET dysfunction.
Myoferlin (MYOF) is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode prote... more Myoferlin (MYOF) is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET). These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin) and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.
The transport of micron-size particles in the lung has important implications for both respirator... more The transport of micron-size particles in the lung has important implications for both respiratory disorders and drug delivery systems. During breathing, the expansion of pulmonary alveoli produces sub-ambient pressures that draw airflow into the lung. The fate of inhaled microparticles during breathing will depend on both particle properties and the complex transient flow fields generated by alveolar wall motion. In
The Eustachian Tube (ET) is a collapsible tube that connects the middle ear to the nasopharynx. D... more The Eustachian Tube (ET) is a collapsible tube that connects the middle ear to the nasopharynx. Dysfunction in the ET leads to a disease called Otitis Media. Our goal is to develop and use fluid-structure interaction (FSI) models of ET opening phenomena to better understand what factors contribute to ET dysfunction in certain patients. We model the ET in COMSOL using geometric data obtained from histological specimens. Using histological data allows us to make anatomically accurate models which are then used to simulate the clinical tests performed on patients. This serves as an excellent validation tool for our COMSOL model. We have created a FSI model of a healthy ET which successfully simulated the large tissue deformations that occur during ET opening. We found that higher order basis functions were required in order to prevent element failure. We are currently extending this model to account for transient dynamics and two-way coupling.
... PATHOPHYSIOLOGY, AND PATHOGENESIS CUNEYT M. ALPER, MD, CHAIR CHARLES D. BLUESTONE, MD, CO-CHA... more ... PATHOPHYSIOLOGY, AND PATHOGENESIS CUNEYT M. ALPER, MD, CHAIR CHARLES D. BLUESTONE, MD, CO-CHAIR BERNARD ARS, MD, PHD SAMIR N. GHADIALI, PHD STEN O. HELLSTRÖM, MD, PHD J. DOUGLAS ...
A primary etiological factor underlying chronic middle ear disease is an inability to open the co... more A primary etiological factor underlying chronic middle ear disease is an inability to open the collapsible Eustachian tube (ET). However, the structure-function relationships responsible for ET dysfunction in patient populations at risk for developing otitis media (OM) are not known. In this study, three-dimensional (3D) finite element (FE) modeling techniques were used to investigate how changes in biomechanical and anatomical properties influence opening phenomena in three populations: normal adults, young children and infants with cleft palate. Histological data was used to create anatomically accurate models and FE techniques were used to simulate tissue deformation and ET opening. Lumen dilation was quantified using a computational fluid dynamic (CFD) technique and a sensitivity analysis was performed to ascertain the relative importance of the different anatomical and tissue mechanical properties. Results for adults suggest that ET function is highly sensitive to tensor veli palatini muscle (TVPM) forces and to periluminal mucosal tissue (PMT) elasticity. Young children and cleft palate subjects exhibited reduced sensitivity to TVPM forces while changes in PMT stiffness continued to have a significant impact on ET function. These results suggest that reducing PMT stiffness might be an effective way to restore ET function in these populations. Varying TVPM force vector relationships via changes in hamulus location had no effect on ET opening in young children and cleft palate subjects but did alter force transmission to the ET lumen during conditions of elevated adhesion. These models have therefore provided important new insights into the biomechanical mechanisms responsible for ET dysfunction.
Myoferlin (MYOF) is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode prote... more Myoferlin (MYOF) is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET). These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin) and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.
The transport of micron-size particles in the lung has important implications for both respirator... more The transport of micron-size particles in the lung has important implications for both respiratory disorders and drug delivery systems. During breathing, the expansion of pulmonary alveoli produces sub-ambient pressures that draw airflow into the lung. The fate of inhaled microparticles during breathing will depend on both particle properties and the complex transient flow fields generated by alveolar wall motion. In
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