TY  - CONF
Y1  - 2024/01/10/
A1  - Hamed, Omar
A1  - Moss, Guy WJ
A1  - Dua, Vivek
AV  - public
KW  - Absorptive
KW  -  Airway
KW  -  Airway Surface Liquid
KW  -  BK Channel
KW  -  CFTR
KW  -  Computational
KW  -  Cystic fibrosis
KW  -  ENaC
KW  -  Epithelia
KW  -  Epithelium
KW  -  Fluid Transport
KW  -  Gap junction
KW  -  Ion channel
KW  -  Ion transport
KW  -  Ionocyte
KW  -  Lung
KW  -  Mathematical
KW  -  Model
KW  -  Modelling
KW  -  Mucociliary Clearance
KW  -  Multicell
KW  -  Multiscale
KW  -  Overexpress
KW  -  Secretory
KW  -  SICM
KW  -  Therapy
KW  -  Drug
KW  -  Mucus
KW  -  Rheology
KW  -  Kaftrio
KW  -  Modulator
KW  -  Trikafta
KW  -  Spinnability
KW  -  CBF
KW  -  Cilia
KW  -  Dyskinesia
KW  -  Nanosensor
KW  -  In vitro
KW  -  In silico
KW  -  Bronchi
KW  -  Bronchial
T2  - BIOREME Network+ Conference: Research at the interface of Mathematical Sciences and Respiratory Medicine
N2  - The airway surface liquid (ASL) is a thin fluid layer (0.1-10 痠) 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.
TI  - Developing and testing a theoretical framework for airway surface liquid homeostasis
M2  - Nottingham, UK
UR  - https://www.bioreme.net/events-all/anwc2024
ID  - discovery10189830
ER  -