Journal article
Local photocrosslinking of native tissue matrix regulates lung epithelial cell mechanosensing and function
Nature materials
05 Sep 2025
PMID: 40913159
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in the extracellular matrix such as aberrant deposition, densification and increased crosslinking are hallmarks of late-stage fibrotic diseases that often lead to organ dysfunction. Biomaterials have been widely used to mimic the mechanical properties of the fibrotic matrix and study pathophysiologic cell function. However, the initiation of fibrosis has largely been overlooked, due to challenges in recapitulating early stages of disease progression within the native extracellular microenvironment. Here, using visible-light-mediated photochemistry, we induced local crosslinking and stiffening of extracellular matrix proteins within ex vivo mouse and human lung tissue. In ex vivo lung tissue of epithelial cell lineage-traced mice, local matrix crosslinking mimicked early fibrotic lesions that increased alveolar epithelial cell mechanosensing, differentiation, and nascent protein deposition and remodelling. However, the inhibition of cytoskeletal tension, mechanosensitive signalling pathways or integrin engagement reduced epithelial cell spreading and differentiation. Our findings emphasize the role of local extracellular matrix crosslinking and nascent protein deposition in early stage tissue fibrosis and have implications for ex vivo disease modelling and applications to other tissues.
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Details
- Title
- Local photocrosslinking of native tissue matrix regulates lung epithelial cell mechanosensing and function
- Creators
- Donia W Ahmed - University of MichiganMatthew L Tan - University of MichiganYuchen Liu - Drexel UniversityJackson Gabbard - University of MichiganEsther Gao - University of MichiganAvinava Roy - University of MichiganMichael M Hu - University of MichiganFiraol S Midekssa - University of MichiganMiriam Stevens - University of MichiganFulei Wuchu - University of MichiganMinal Nenwani - University of MichiganJingyi Xia - University of MichiganAdam Abraham - University of MichiganDeepak Nagrath - University of MichiganLin Han - Drexel UniversityRachel L Zemans - University of MichiganBrendon M Baker - University of MichiganClaudia Loebel (Corresponding Author) - University of Pennsylvania
- Publication Details
- Nature materials
- Publisher
- Nature Publishing Group
- Number of pages
- 33
- Grant note
- R56ES035710 / U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) CMMI-1751898 / National Science Foundation (NSF) IA-939940 / American Lung Association (Lung Association) T32 HL007749 / NHLBI NIH HHS R00-HL151670 / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35HL160770 / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35GM157063 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001564645900001
- Scopus ID
- 2-s2.0-105015467284
- Other Identifier
- 991022094543604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Physical
- Materials Science, Multidisciplinary
- Physics, Applied
- Physics, Condensed Matter