Document Detail


Effect of Substrate Stiffness on Pulmonary Fibroblast Activation by TGF-β
MedLine Citation:
PMID:  22446029     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Peptide crosslinkers containing the sequence C-X-CG (X represents various adhesive peptides) were incorporated into PEG hydrogel networks with different mechanical properties. Pulmonary fibroblasts (PFs) exhibit increased adhesion to rigid hydrogels modified with X=RGDS, DGEA and IKVAV (0.5 and/or 5 mM) compared to a scrambled control (X=HRPNS). PFs exhibit increased adhesion to softer hydrogels when X=DGEA at low (0.5 mM) peptide concentration. PFs seeded onto hydrogels modified with X=RGDS produce alpha-smooth muscle actin (α-SMA), a myofibroblast marker, and form an extensive cytoskeleton with focal adhesions. Decreasing substrate stiffness (achieved through hydrolytic degradation) results in downregulation of α-SMA expression by PFs. Substrate stiffness increases the sensitivity of PFs to exogenously applied transforming growth factor beta (TGF-β1); PFs on the most rigid gels (E=900 kPa) express α-SMA when treated with low concentrations of TGF-β1 (1 ng/mL)while those on less rigid gels (E=20-60 kPa) do not. These results demonstrate the importance of both mechanical and chemical cues in studying pulmonary fibroblast activation and establish PEG hydrogels as a viable material for further studying IPF etiology.
Authors:
Helena N Chia; Marina Vigen; Andrea M Kasko
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-20
Journal Detail:
Title:  Acta biomaterialia     Volume:  -     ISSN:  1878-7568     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Biomedical Engineering Interdepartmental Program, University of California, Los Angeles, CA 90095 United States.
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