Biomimetic Substrate to Probe Dynamic Interplay of Topography and Stiffness on Cardiac Fibroblast Activation

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Author(s)Cao, Zheng
Author(s)Ball, Jacob K.
Author(s)Lateef, Ali H.
Author(s)Virgile, Connor P.
Author(s)Corbin, Elise A.
Date Accessioned2023-04-14T13:16:35Z
Date Available2023-04-14T13:16:35Z
Publication Date2023-02-14
DescriptionThis article was originally published in ACS Omega. The version of record is available at: https://doi.org/10.1021/acsomega.2c06529. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c06529
AbstractMaterials with the ability to change properties can expand the capabilities of in vitro models of biological processes and diseases as it has become increasingly clear that static, stiff materials with smooth surfaces fall short in recapitulating the in vivo cellular microenvironment. Here, we introduce a patterned material that can be rapidly stiffened and softened in situ in response to an external magnetic field through the addition of magnetic inclusions into a soft silicone elastomer with topographic surface patterning. This substrate can be used for cell culture to investigate short-term cellular responses to dynamic stiffening or softening and the interaction with topography that encourages cells to assume a specific morphology. We investigated short-term cellular responses to dynamic stiffening or softening in human ventricular cardiac fibroblasts. Our results indicate that the combination of dynamic changes in stiffness with and without topographic cues induces different effects on the alignment and activation or deactivation of myofibroblasts. Cells cultured on patterned substrates exhibited a more aligned morphology than cells cultured on flat material; moreover, cell alignment was not dependent on substrate stiffness. On a patterned substrate, there was no significant change in the number of activated myofibroblasts when the material was temporally stiffened, but temporal softening caused a significant decrease in myofibroblast activation (50% to 38%), indicating a competing interaction of these characteristics on cell behavior. This material provides a unique in vitro platform to observe the time-dependent dynamics of cells by better mimicking more complex behaviors and realistic microenvironments for investigating biological processes, such as the development of fibrosis.
SponsorThis research was supported in part by the Delaware INBRE program (P20 GM103446), the Institutional Development Award (U54 GM104941), and the Delaware Center for Musculoskeletal Research COBRE (P20 GM139760), with grants from the National Institute of General Medical Science from the National Institutes of Health and the State of Delaware.
CitationCao, Zheng, Jacob K. Ball, Ali H. Lateef, Connor P. Virgile, and Elise A. Corbin. “Biomimetic Substrate to Probe Dynamic Interplay of Topography and Stiffness on Cardiac Fibroblast Activation.” ACS Omega 8, no. 6 (February 14, 2023): 5406–14. https://doi.org/10.1021/acsomega.2c06529.
ISSN2470-1343
URLhttps://udspace.udel.edu/handle/19716/32648
Languageen_US
PublisherACS Omega
Keywordselastomers
Keywordsmagnetic properties
Keywordsmaterials
Keywordsstiffness
Keywordssubstrates
TitleBiomimetic Substrate to Probe Dynamic Interplay of Topography and Stiffness on Cardiac Fibroblast Activation
TypeArticle
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