Details:

Alternative Title:
Sci Rep
Publisher's site:
http://dx.doi.org/10.1038/srep06425
Personal Author:
Young, Jennifer L. ; Kretchmer, Kyle ; Ondeck, Matthew G. ; Zambon, Alexander C. ; Engler, Adam J.
Young, Jennifer L. ; Kretchmer, Kyle ; Ondeck, Matthew G. ; Zambon, Alexander C. ; Engler, Adam J. Less -
Description:
Cells secrete and assemble extracellular matrix throughout development, giving rise to time-dependent, tissue-specific stiffness. Mimicking myocardial matrix stiffening, i.e. ~10-fold increase over 1 week, with a hydrogel system enhances myofibrillar organization of embryonic cardiomyocytes compared to static hydrogels, and thus we sought to identify specific mechanosensitive proteins involved. Expression and/or phosphorylation state of 309 unique protein kinases were examined in embryonic cardiomyocytes plated on either dynamically stiffening or static mature myocardial stiffness hydrogels. Gene ontology analysis of these kinases identified cardiogenic pathways that exhibited time-dependent up-regulation on dynamic versus static matrices, including PI3K/AKT and p38 MAPK, while GSK3β, a known antagonist of cardiomyocyte maturation, was down-regulated. Additionally, inhibiting GSK3β on static matrices improved spontaneous contraction and myofibril organization, while inhibiting agonist AKT on dynamic matrices reduced myofibril organization and spontaneous contraction, confirming its role in mechanically-driven maturation. Together, these data indicate that mechanically-driven maturation is at least partially achieved via active mechanosensing at focal adhesions, affecting expression and phosphorylation of a variety of protein kinases important to cardiomyogenesis.
Subjects:
[+]
Article
Source:
Sci Rep. 2014; 4.
Pubmed ID:
25236849
Pubmed Central ID:
PMC4168277
Document Type:
Journal Article
Funding:
1U54HK08460 A/HK/PHITPO CDC HHS/United States ; R21HL106529/HL/NHLBI NIH HHS/United States
1U54HK08460 A/HK/PHITPO CDC HHS/United States ; R21HL106529/HL/NHLBI NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:e71a1cf5b086dd00d5e21d773e1cd8778d563d6a4e17d395a3d24b34d5a317c2
Download URL:
https://stacks.cdc.gov/view/cdc/32197/cdc_32197_DS1.pdf
File Type:

Supporting Files

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