Fluid shear stress plays a pivotal role in regulating cellular behaviors, maintaining tissue homeostasis, and driving disease progression. Cells in various tissues are specifically adapted to physiological levels of shear stress and exhibit sensitivity to variations in its magnitude, highlighting the requirement for a comprehensive understanding of cellular responses to both physiologically and pathologically relevant levels of shear stress. In this study, we developed an independent upstream flow-resistance module with high fluidic resistances comprising three microchannels. The validity of the flow-resistance module was confirmed via computational fluid dynamics (CFD) simulations and flow calibration experiments, resulting in the generation of steady wall shear stresses ranging from 0.06 to 11.57 dyn/cm within the interconnected cell culture chips. Gene expression profiles, cytoskeletal remodeling, and morphological changes, as well as Yes-associated protein (YAP) nuclear translocation, were investigated in response to various shear stresses to authenticate the reliability of our experimental platform, indicating an increasing trend as the shear stress increases, reaching its maximum at various shear stresses. Our findings suggest that this flow-resistance module can be readily employed for precise characterization of cellular responses under various shear stresses.
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http://dx.doi.org/10.1021/acsbiomaterials.4c01604 | DOI Listing |
Sci Adv
January 2025
Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, CT 06511, USA.
Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low shear stress (LSS), physiological shear stress (PSS), high shear stress (HSS), and oscillatory shear stress (OSS) that induce vessel inward remodeling, stabilization, outward remodeling, or disease susceptibility, respectively. Combined with a publicly available database on EC transcriptomic responses to drug treatments, this approach inferred a regulatory network controlling EC states and made several notable predictions.
View Article and Find Full Text PDFClin Oral Investig
January 2025
Department of Restorative Dentistry, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
Objectives: To evaluate the shear bond strength (SBS) of universal cements (UCs) to dentin prepared with different diamond burs using various adhesive strategies.
Materials And Methods: One-hundred-twenty molars were prepared to expose the mid-coronal dentin. The teeth were divided into two groups according to diamond bur preparations: coarse and super-fine grit burs.
Alzheimers Dement
December 2024
University of Toronto, Toronto, ON, Canada.
Background: Drug discovery efforts in neurological diseases, such as Alzheimer's disease (AD), have had particularly poor outcomes due to the lack of models that capture the cerebral vasculature. There is an unmet need to develop models that capture the physiological challenge of overcoming the blood-brain barrier (BBB) and impacts of blood flow-induced shear stress. In this work, we use a microfluidic platform to model the cerebral vasculature in familial AD (fAD) using patient-derived brain endothelial-like cells (BECs) and neurons.
View Article and Find Full Text PDFPulmonary artery (PA) flow analysis is crucial for understanding the progression of pulmonary hypertension (PH). We hypothesized that PA flow characteristics vary according to PH etiology. In this study, we used 4D flow cardiovascular magnetic resonance imaging (CMR) to compare PA flow velocity and wall shear stress (WSS) between patients with pulmonary arterial hypertension (PAH) and those with heart failure with preserved ejection fraction and pulmonary hypertension (PH-HFpEF).
View Article and Find Full Text PDFCureus
December 2024
Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, JPN.
Lip ulcers associated with endotracheal tube fixation are a known complication in adults, but their prevalence in neonates and preterm infants remains unclear. We report a case of a right oral commissure ulcer that developed during endotracheal tube fixation at the right oral commissure and left lateral decubitus positioning in an extremely preterm infant with unilateral pulmonary interstitial emphysema (PIE). A male infant was born at 24 weeks and four days of gestation, weighing 696 gm.
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