The micromechanics of lung alveoli: structure and function of surfactant and tissue components

Abstract

The mammalian lung´s structural design is optimized to serve its main function: gas exchange. It takes place in the alveolar region (parenchyma) where air and blood are brought in close proximity over a large surface. Air reaches the alveolar lumen via a conducting airway tree. Blood flows in a capillary network embedded in inter-alveolar septa. The barrier between air and blood consists of a continuous alveolar epithelium (a mosaic of type I and type II alveolar epithelial cells), a continuous capillary endothelium and the connective tissue layer in-between. By virtue of its respiratory movements, the lung has to withstand mechanical challenges throughout life. Alveoli must be protected from over-distension as well as from collapse by inherent stabilizing factors. The mechanical stability of the parenchyma is ensured by two components: a connective tissue fiber network and the surfactant system. The connective tissue fibers form a continuous tensegrity (tension + integrity) backbone consisting of axial, peripheral and septal fibers. Surfactant (surface active agent) is the secretory product of type II alveolar epithelial cells and covers the alveolar epithelium as a biophysically active thin and continuous film. Here, we briefly review the structural components relevant for gas exchange. Then we describe our current understanding of how these components function under normal conditions and how lung injury results in dysfunction of alveolar micromechanics finally leading to lung fibrosis.

Airway macrophages as the guardians of tissue repair in the lung

“…One of the key functions of AM in the lung at steady state is to regulate surfactant homeostasis which is crucial for healthy lung function and immunity. Surfactant is a key lipoprotein that reduces surface tension at the air–liquid interface preventing alveolar collapse . In this respect, GM‐CSF upregulates peroxisome proliferator‐activated receptor (PPAR‐γ) expression in AM and the GM‐CSFR–PPAR‐γ axis is a critical molecular pathway essential not only for AM development but also for lung homeostasis by promoting surfactant catabolism .…”

“…Surfactant is a key lipoprotein that reduces surface tension at the air-liquid interface preventing alveolar collapse. 15 In this respect, GM-CSF upregulates peroxisome proliferator-activated receptor (PPAR-c) expression in AM and the GM-CSFR-PPAR-c axis is a critical molecular pathway essential not only for AM development but also for lung homeostasis by promoting surfactant catabolism. 13 At steady state, AM remain in an immunosuppressed state, and their development, maintenance and phenotype are tightly controlled by additional local signals in the lung.…”

Second-generation lung-on-a-chip array with a stretchable biological membrane

“…Here, we present a second-generation lung-on-a-chip with an array of alveoli and a stretchable biological membrane that mimics in vivo functionality at an unprecedented level. The CEmembrane reproduces the composition and geometrical, biophysical, mechanical and transport properties of the lung alveolar barrier 28 . It recreates the native viscoelastic microenvironment of the cells.…”

“…The lung parenchyma comprises of a large number of tiny alveoli organised in a threedimensional architecture. Thin alveolar walls made of capillary networks and connective tissue separate the alveoli and stabilise the parenchymal construction 27,28 . This complex and dynamic environment makes the lung alveolar unique and difficult to mimic in vitro.…”

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

“…The thick side of the ACM is where the cell nuclei and fiber network are concentrated, providing mechanical stability and regenerative potential, while the thin side is where the alveolar epithelium and capillary endothelium share the same basal lamina membrane. In human lung, one half of the ACM is thin, underscoring the fragility of the ACM as well as its strength to support an organ that during inflation contains 80% air, 10% tissue, and 10% blood (Knudsen and Ochs, 2018). Although epithelial, endothelial, and interstitial cells can generate forces, the contribution of the lung extracellular matrix (ECM) dominates, as shown by only minimal changes in the strain and elastic recoil of the lung ECM after decellularization (Nonaka et al, 2014).…”