Multiscale stiffness of human emphysematous precision cut lung slices
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Date
2023-05-19
Authors
Kim, Jae Hun
Schaible, Niccole
Hall, Joseph K.
Bartolák-Suki, Erzsébet
Deng, Yuqing
Herrmann, Jacob
Sonnenberg, Adam
Behrsing, Holger P.
Lutchen, Kenneth R.
Krishnan, Ramaswamy
Version
Published version
OA Version
Citation
J.H. Kim, N. Schaible, J.K. Hall, E. Bartolák-Suki, Y. Deng, J. Herrmann, A. Sonnenberg, H.P. Behrsing, K.R. Lutchen, R. Krishnan, B. Suki. 2023. "Multiscale stiffness of human emphysematous precision cut lung slices." Science Advances, Volume 9, Issue 20, pp.eadf2535-. https://doi.org/10.1126/sciadv.adf2535
Abstract
Emphysema is a debilitating disease that remodels the lung leading to reduced tissue stiffness. Thus, understanding 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 designed 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 computational 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 mechanical forces, lead to rupture and structural deterioration of the emphysematous lung parenchyma.
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Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)