Water Sorption and Structural Properties of Human Airway Mucus in Health and Muco-Obstructive Diseases.

Muco-obstructive diseases change airway mucus properties, impairing mucociliary transport and increasing the likelihood of infections. To investigate the sorption properties and nanostructures of mucus in health and disease, we investigated mucus samples from patients and cell cultures (cc) from healthy, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) airways. Atomic force microscopy (AFM) revealed mucin monomers with typical barbell structures, where the globule to spacer volume ratio was the highest for CF mucin. Accordingly, synchrotron small-angle X-ray scattering (SAXS) revealed more pronounced scattering from CF mucin globules and suggested shorter carbohydrate side chains in CF mucin and longer side chains in COPD mucin. Quartz crystal microbalance with dissipation (QCM-D) analysis presented water sorption isotherms of the three types of human airway mucus, where, at high relative humidity, COPD mucus had the highest water content compared to cc-CF and healthy airway mucus (HAM). The higher hydration of the COPD mucus is consistent with the observation of longer side chains of the COPD mucins. At low humidity, no dehydration-induced glass transition was observed in healthy and diseased mucus, suggesting mucus remained in a rubbery state. However, in dialyzed cc-HAM, a sorption-desorption hysteresis (typically observed in the glassy state) appeared, suggesting that small molecules present in mucus suppress the glass transition.

Collagen Fibril Intermolecular Spacing Changes with 2-Propanol: A Mechanism for Tissue Stiffness.

Materials composed primarily of collagen are important as surgical scaffolds and other medical devices and require flexibility. However, the factors that control the suppleness and flexibility of these materials are not well understood. Acellular dermal matrix materials in aqueous mixtures of 2-propanol were studied. Synchrotron-based small-angle X-ray scattering was used to characterize the collagen structure and structural arrangement. Stiffness was measured by bend tests. Bend modulus increased logarithmically with 2-propanol concentration from 0.5 kPa in water to 103 kPa in pure 2-propanol. The intermolecular spacing between tropocollagen molecules decreased from 15.3 to 11.4 Å with increasing 2-propanol concentration while fibril diameter decreased from 57.2 to 37.2 nm. D-spacing initially increased from 63.6 to 64.2 nm at 50% 2-propanol then decreased to 60.3 nm in pure 2-propanol. The decrease in intermolecular spacing and fibril diameter are due to removal of water and the collapse of the hydrogen bond structure between tropocollagen molecules causing closer packing of the molecules within a fibril. We speculate this tighter molecular packing may restrict the sliding of collagen within fibrils, and similar disruption of the extended hydration layer between fibrils may lead to restriction of sliding between fibrils. This mechanism for tissue stiffness may be more general.