Year: 2018
Type: article
Abstract: Lung function is inherently mechanical in nature and depends on the capacity to conduct air and blood to and from the gas exchange regions. Variations in the elastic properties of the human lung across anatomical compartments and with aging are likely important determinants of lung function but remain relatively poorly characterized. Here we applied atomic force microscopy microindentation to characterize human lung tissue from subjects ranging in age from 11 to 60 yr old. We observed striking anatomical variations in elastic modulus, with the airways (200- to 350-µm diameter) the stiffest and the parenchymal regions the most compliant. Vessels (diameter < 100 µm) represented an intermediate mechanical environment and displayed diameter-dependent trends in elastic modulus. Binning our samples into younger (11-30 yr old) and older (41-60 yr old) groups, we observed significant age-related increases in stiffness in parenchymal and vessel compartments, with the most pronounced changes in the vessels. To investigate cellular mechanisms that might contribute to vascular stiffening with aging, we studied primary human pulmonary artery smooth muscle cells from subjects ranging in age from 11 to 60 yr old. While we observed no change in the mechanical properties of the cells themselves, we did observe trends toward increases in traction forces and extracellular matrix deposition with aging. These results demonstrate age-related changes in tissue mechanical properties that likely contribute to impaired lung function with aging and underscore the potential to identify mechanisms that contribute to mechanical tissue remodeling through the study of human cells and tissues from across the aging spectrum.
Institutions: Mayo Clinic, Brigham and Women's Hospital
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Arterial Stiffness in the Pathogenesis of Human Pulmonary Arterial Hypertension, Mechanotransduction and YAP/TAZ Signaling in Pulmonary Arterial Hypertension, G3154139807, Mechanobiology of Vascular Remodeling in Pulmonary Arterial Hypertension, G4267322586, Targeting matrix stiffness in lung and liver fibrosis, Epithelial-Mesenchymal Interactions in Fibrosis Resolution, Pulmonary Hypertension Breakthrough Initiative, G9000067856
OpenAlex ID: W2788966615