Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury.

The link between the structural organization of the fibrillar components of lung extracellular matrix (ECM), local tissue stiffness and global viscoelastic behaviour is not known. Here we investigated the effect of injurious mechanical ventilation on the local lung tissue stiffness using 4D synchrotron phase-contrast micro-CT, in normal lung and 7 days after intratracheal bleomycin induced lung injury in anesthetized rats. Quantitative maps of local lung strain (ε) were computed within aerated lung acini, using a stepwise image registration method. Fibrillar organization of collagen and elastin at the nanoscale was measured using synchrotron small-angle x-ray scattering (SAXS). Local microscopic tissue ε was reduced in the aerated acini of normal lungs post injurious ventilation and in bleomycin-injured lungs and was associated with an increase in dynamic elastance (H). The scattering peak angle (q) which is inversely related to fibril D-spacing, was decreased by injurious ventilation indicating an elongation of the collagen fibril spacing in both normal and bleomycin-injured lung. There was a positive relationship between collagen periodicity and global tissue elastance, while an inverse relation was observed with tissue hysteresis. Our data demonstrate the effect of both bleomycin-induced lung injury and high-strain mechanical ventilation on the nanoscale fibrillar organization of collagen and for the first time, a link between collagen D-spacing and global lung tissue stiffening and viscoelastic behaviour.