Chapter 2: Advances in Lung Developmental Mechanobiology

The lung contains both epithelial and mesenchymal cell types. Lung epithelial cells are characteristically localized at the interface between the organism and the environment and have many critical and vital functions such as the fluid balance, barrier protection, particulate clearance, production of both mucus and surfactants, and immune response initiation as well as tissue repair after injury. Lung cells are continuously exposed to mechanical stresses during their development and function. For example, lung epithelial cells are continuously exposed to varying levels of mechanical stresses due to lung’s complex structure and the cyclic deformation of the lung during the respiratory cycle. The normal functions of the lung are maintained under these tightly regulated conditions, and changes in mechanical stresses may profoundly affect different functions of lung cells and therefore the overall lung functions. A major goal of lung mechanobiology is to understand how the mechanical behavior of the lung emerges from its cellular and molecular constituents. The central role of mechanics in the lung function was revealed with the help of the rapid progress in seminal historical developments, including both the identification and characterization of the functions of lung surfactants. In this chapter, we will describe the effects of mechanical factors on lung development, and how the airway peristalsis affects lung development. In addition, we will describe the functional roles of parathyroid hormone-related protein (PTHrP) in lung development and stretch transduction, as well as the functions of extracellular calcium-sensing receptor (CaSR) in fetal lung development.