Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue

Abstract

Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers. We measured the quasi-static, uniaxial stress-strain curves of lung tissue sheets in hypotonic, normal, and hypertonic solutions. We found that the stress-strain curve was sensitive to osmolarity, but this sensitivity decreased after proteoglycan digestion. Images of immunofluorescently labeled collagen networks showed that the fibers follow the alveolar walls that form a hexagonal-like structure. Despite the large heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased linearly with osmolarity. We developed a two-dimensional hexagonal network model of the alveolar structure incorporating the mechanical properties of the collagen-elastin fibers and their interaction with proteoglycans. The model accounted for the stress-strain curves observed under all experimental conditions. The model also predicted how aspect ratio changed with osmolarity and strain, which allowed us to estimate the Young's modulus of a single alveolar wall and a collagen fiber. We therefore identify a novel and important role for the proteoglycans: they stabilize the collagen-elastin network of connective tissues and contribute to lung elasticity and alveolar stability at low to medium lung volumes.

Quantification of Extracellular Matrix Proteins from a Rat Lung Scaffold to Provide a Molecular Readout for Tissue Engineering

“…Glycoproteins and proteoglycans are important to the viscoelastic behavior of the tissue and stabilize the collagen and elastin networks, thereby contributing to the maintenance of overall tissue architecture. Removal of proteoglycans tends to result in "softer" tissue as evidenced by decreased stress per unit strain, though this is somewhat less important than the contribution of fibrillar collagen networks throughout the tissue (71). Fibrillar collagens are largely responsible for the ultimate tensile strength of organs; the apparent preservation of these proteins suggests that the tensile mechanics should be relatively similar between native and decellularized lungs.…”

Micro-Mechanical Characterization of Lung Tissue Using Atomic Force Microscopy

“…Invasive methods such as the one described here alter the lung architecture in important ways through the loss of the air-liquid interface that normally exists in the air-filled lung and the loss of pre-stress that maintains lung partial inflation upon relaxation of respiratory muscles. These limitations are common to all measurements made in lung tissue strips 18 . Notably, however, the median stiffness measured in the parenchyma of normal lung tissue (shear modulus ~0.5kPa) does not differ substantially from estimates based on punch-indentation of intact lungs at resting volumes 19,20 .…”

Changes in versican and chondroitin sulfate proteoglycans during structural development of the lung

“…The high anionic charge density of PGs, such as versican, attracts mobile counterions, which, in turn, generate an osmotic gradient promoting the retention of water. As a result, PGs contribute to interstitial tissue volumes, provide tissue resilience, and influence tissue mechanics (6,9,20,25,30). We hypothesized that a reduction in versican content or a change to its microstructure, particularly to the CS side chains leading to a decrease in anionic charge density, may account for the decrease in lung tissue volumes that characterize structural development of the lung in late gestation.…”