Mechanical forces and mechanically induced signal transduction in the alveolar epithelium
Supervisor: M. Frick
Intact alveoli are the functional units of the lung and are vital for proper lung function. Complex inter- and intracellular signals within cells of the alveolar air - blood barrier (epithelial cells , endothelial cells) are essential for maintaining the alveolar integrity and homeostasis. It is well established that mechanical forces, e.g. resulting from ventilation, play a key role in generation of these signals. Distension of alveolar epithelal cells results in intracellular calcium signals and stimulates secretion of pulmonary surfactant. Surfactant is essential to lower surface tension at the respiratory air-liquid interface – a decisive function in lung biomechanics - facilitating inspiration and preventing collapse of alveoli.
However, due to the complex architecture of the alveoli (air - water interface , mechanical strain) it has not been possible yet to investigate in molecular detail 1) how mechanical forces affect different cell types of the alveolar barrier, 2) how individual cells / cell types sense these forces and 3) how intra- and intercellular signaling and integration of these signals results in regulated surfactant secretion within individual alveoli.
The aim of this project is therefore to use new cell culture models that allow to mimick the complex microenvironment of an intact alveolus whilst simultaneously studying and manipulating the mechanical forces, and to combine these with high-resolution fluorescence microscopy, cell and molecular biology tools to answer these questions.
- J Cell Sci. (2015); 128(6):1193-203
- J Cell Sci. (2014); 127(24):5218-27
- FASEB J. (2013); 27(4):1772-83
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- Proc. Natl. Acad. Sci. (2011); 108(35):14503-8.