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Developing and testing a theoretical framework for airway surface liquid homeostasis

Hamed, Omar; Moss, Guy WJ; Dua, Vivek; (2024) Developing and testing a theoretical framework for airway surface liquid homeostasis. Presented at: BIOREME Network+ Conference: Research at the interface of Mathematical Sciences and Respiratory Medicine, Nottingham, UK. Green open access

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Abstract

The airway surface liquid (ASL) is a thin fluid layer (0.1-10 µm) lining the airway epithelium which plays several important roles in normal lung function. These include preventing collapse of the alveoli and small airways during exhalation and facilitating mucociliary clearance of mucus-trapped pathogens in the upper airways. ASL homeostasis is regulated by a complex synergy of ion channels, transporters, and tight junction proteins. When this balance is disrupted, it can result in diseases such as pulmonary oedema and cystic fibrosis. Existing mathematical models of ASL homeostasis typically treat the system as a single idealised cell. These single-cell models attempt to capture the co-ordination of active transport, channel-mediated electrodiffusion and paracellular flux, creating osmotic gradients for water flux, providing quantitative explanations of specific ion and fluid transport processes. However, airway epithelium consists of several distinct cell types, each with specialised functions. To quantitatively and systematically analyse how different cell types contribute to ASL regulation, we developed a multicellular computational modelling framework for fluid and ion flux in airway epithelia. This was then specifically solved and analysed across multiple multicell modelling scenarios to understand the bioelectric properties of the epithelium and suggest therapeutic targets for ASL restoration in diseased states. Additionally, we cultured human bronchial airway epithelia in the laboratory to measure key airway epithelial characteristics, including transepithelial potential difference and ASL depth, which could be used to validate the model. These were measured with precision using nanosensor probes mounted on a scanning ion conductance microscope. This system was also used to measure mucus rheology and cilia beat frequency, further properties associated with airway disease pathology, to quantify the effectiveness of therapeutic target modulation in cystic fibrosis airway models.

Type: Conference item (Presentation)
Title: Developing and testing a theoretical framework for airway surface liquid homeostasis
Event: BIOREME Network+ Conference: Research at the interface of Mathematical Sciences and Respiratory Medicine
Location: Nottingham, UK
Dates: 10 - 11 January 2024
Open access status: An open access version is available from UCL Discovery
Publisher version: https://www.bioreme.net/events-all/anwc2024
Language: English
Keywords: Absorptive, Airway, Airway Surface Liquid, BK Channel, CFTR, Computational, Cystic fibrosis, ENaC, Epithelia, Epithelium, Fluid Transport, Gap junction, Ion channel, Ion transport, Ionocyte, Lung, Mathematical, Model, Modelling, Mucociliary Clearance, Multicell, Multiscale, Overexpress, Secretory, SICM, Therapy, Drug, Mucus, Rheology, Kaftrio, Modulator, Trikafta, Spinnability, CBF, Cilia, Dyskinesia, Nanosensor, In vitro, In silico, Bronchi, Bronchial
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10189830
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