Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization
Hao Ma, Anouk Killaars, Frank W. DelRio, Chun Yang, Kristi S. Anseth
Valvular interstitial cells (VICs) are key regulators of the heart valve's extracellular matrix (ECM), and upon tissue damage, quiescent VIC fibroblasts become activated to myofibroblasts. As the behavior of VICs during disease progression and wound healing is different compared to healthy tissue, we hypothesized that the organization of the matrix mechanics, which results from depositing of collagen fibers, would affect VIC phenotypic transition. Specifically, we investigated how the subcellular organization of matrix mechanical properties affects expression of Yes-associated protein (YAP), a mechanical sensor, and alpha-smooth muscle actin (alpha-SMA), a myofibroblast marker, in VICs. Photo-tunable hydrogels were used to generate substrates with different moduli and to create organized and disorganized patterns of varying elastic moduli. When VICs were cultured on these matrices, YAP and alpha-SMA activation were significantly increased on substrates with higher elasticity or a higher percentage of stiff regions. Moreover, VICs cultured on substrates with a spatially disorganized elasticity had smaller focal adhesions, less nuclear localized YAP, less alpha-SMA organization into stress fibers and higher proliferation compared to those cultured on substrates with a regular mechanical organization. Collectively, these results suggest that disorganized spatial variations in mechanics that appear during wound healing and fibrotic disease progression may influence the maintenance of the VIC fibroblast phenotype, causing more proliferation, ECM remodeling and matrix deposition.
, Killaars, A.
, DelRio, F.
, Yang, C.
and Anseth, K.
Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization, Biomaterials, [online], https://doi.org/10.1016/j.biomaterials.2017.03.040, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=922681
(Accessed December 3, 2023)