A76-15 Mechanics of Single Collagen Fibers From Human Healthy and COPD Lungs

Abstract Introduction Collagen fibers are key load-bearing components of lung tissue that protect against mechanical failure by generating gradually increasing forces during straightening of wavy fibrils aligned in parallel in the fibers. Emphysema, characterized by alveolar wall rupture and airspace enlargement, is an important component of COPD. We hypothesize that wall rupture in emphysema is due to the altered mechanics at the collagen fiber level. To test this, we isolated individual collagen fibers from human lung precision-cut lung slices (hPCLS) obtained from healthy and COPD donors and measured the fiber stress-strain behavior using a custom-built fiber tensile testing device. Methods The hPCLS were decellularized and digested with elastase following established protocols 1. Individual collagen fibers were mechanically isolated from the remaining collagen network and mounted into the fiber stretcher system for quasi-static tensile testing. Fiber diameter distribution was measured from microscopic images, and the fiber boundary was traced along its length to obtain the fiber profile, from which the harmonic mean of the fiber diameter was calculated from this distribution and used to determine fiber stress. The fiber diameter, and the stress-strain curves were obtained for individual fibers through quasi-static stretching in PBS solution. Fiber mechanics and morphology were compared between healthy and COPD samples. Resultsand Conclusions The diameter variance shows no difference between healthy and COPD (fig. 1b). A nonlinear stress-strain behavior in fig. 1a demonstrated the recruitment process of collagen fibrils during fiber stretching. The COPD stress-strain curves exhibited a wider longer recruitment regime, indicating wavier fibrils and compromised mechanics of the remodeled COPD fibers. Interestingly, there was no significant difference in linear stiffness or diameter distributions between healthy and COPD. These results have implications for emphysema progression, which is associated with rupture of alveolar walls and underlying collagen fibers. REFERENCES: 1 Y Deng et al, Sci Rep 14, 29008, 2024. Figure 1. (a) stress-strain curves of individual collagen fibers obtained from healthy(n=20) and COPD (n=12) lungs. (b) Fiber diameter variance around harmonic mean of the diameter. This abstract is funded by: None