Impact of mechanical signals on human foetal lung cell differentiation
type: CreativeWork
description: A major function of the lung is as a mechanical pump to bring oxygen-rich air into the body, allow gas exchange to occur, and remove carbon dioxide-rich air. It is increasingly recognized that physical forces, such as tension, compression, or shear, as well as passive mechanical material properties such as substrate stiffness affect lung development and play a role in many lung diseases. If the foetal breathing movements leading to amniotic fluid inhalation, and therefore the exertion of physical forces on the developing lung, are perturbed this leads to pulmonary hypoplasia and can result in neonatal morbidity and mortality. Part of the mechanism for these effects is that the sheer stress exerted by the amniotic fluid plays a role in alveolar differentiation as the pressure allows alveolar type I cells to flatten. In humans, mechanical forces and material properties are clinically important both in development, evident in prematurely delivered infants as well as in diseases such as pulmonary fibrosis, where increase in tissue stiffness leads to lung dysfunction. However, not all mechanical cues affecting lung development and disease are known, nor their mechanism of action. There are different biological materials deposited along the proximal-distal axis in the lung, such as cartilage in the trachea and smooth muscle in the bronchi, versus elastic fibres in the alveoli. Considering this, as well as the clinical relevance of stiffness in lung diseases, I hypothesised that tissue stiffness can play a role in defining cellular fate. I measured the stiffness of human embryonic lung slices over developmental time using Atomic Force microscopy-based indentation measurements and found both temporal and spatial stiffness gradients. The spatial gradient revealed that the epithelial tips of the growing airway tubes are softer than the main body of the airway tubes. This contrasted with the closely aligned blood vessels, which did not show significant changes spatially in sti…
abstract: A major function of the lung is as a mechanical pump to bring oxygen-rich air into the body, allow gas exchange to occur, and remove carbon dioxide-rich air. It is increasingly recognized that physical forces, such as tension, compression, or shear, as well as passive mechanical material properties such as substrate stiffness affect lung development and play a role in many lung diseases. If the foetal breathing movements leading to amniotic fluid inhalation, and therefore the exertion of physical forces on the developing lung, are perturbed this leads to pulmonary hypoplasia and can result in neonatal morbidity and mortality. Part of the mechanism for these effects is that the sheer stress exerted by the amniotic fluid plays a role in alveolar differentiation as the pressure allows alveolar type I cells to flatten. In humans, mechanical forces and material properties are clinically important both in development, evident in prematurely delivered infants as well as in diseases such as pulmonary fibrosis, where increase in tissue stiffness leads to lung dysfunction. However, not all mechanical cues affecting lung development and disease are known, nor their mechanism of action. There are different biological materials deposited along the proximal-distal axis in the lung, such as cartilage in the trachea and smooth muscle in the bronchi, versus elastic fibres in the alveoli. Considering this, as well as the clinical relevance of stiffness in lung diseases, I hypothesised that tissue stiffness can play a role in defining cellular fate. I measured the stiffness of human embryonic lung slices over developmental time using Atomic Force microscopy-based indentation measurements and found both temporal and spatial stiffness gradients. The spatial gradient revealed that the epithelial tips of the growing airway tubes are softer than the main body of the airway tubes. This contrasted with the closely aligned blood vessels, which did not show significant changes spatially in sti…
author: Sokleva, Vanesa
language: eng
keywords: alveolar, contractility, hydrogels, mechanobiology, nucleocytoplasmic transport, organoids, SOX9, SpC
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d92d9e64-346e-4eb6-b321-5e625f23a26d/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-12-30
date modified: 2026-07-22T22:24:10Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.97143