Multiscale stiffness of human emphysematous precision cut lung slices

Emphysema is a debilitating disease that remodels the lung leading to reduced tissue stiffness. Thus, under-standing emphysema progression requires assessing lung stiffness at both the tissue and alveolar scales. Here, we introduce an approach to determine multiscale tissue stiffness and apply it to precision-cut lung slices (PCLS). First, we established a framework for measuring stiffness of thin, disk-like samples. We then de-signed a device to verify this concept and validated its measuring capabilities using known samples. Next, we compared healthy and emphysematous human PCLS and found that the latter was 50% softer. Through com-putational network modeling, we discovered that this reduced macroscopic tissue stiffness was due to both microscopic septal wall remodeling and structural deterioration. Lastly, through protein expression profiling, we identified a wide spectrum of enzymes that can drive septal wall remodeling, which, together with mechan-ical forces, lead to rupture and structural deterioration of the emphysematous lung parenchyma.

Automated summary

By measuring tissue stiffness at both the tissue and alveolar scales, we found that the lung tissue of patients with emphysema was 50% softer due to microscopic septal wall remodeling and structural deterioration. Protein expression profiling revealed a wide range of enzymes involved in septal wall remodeling, along with mechanical forces, leading to rupture and structural deterioration of the emphysematous lung parenchyma.