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Interrogating cardiac muscle cell mechanobiology on stiffness gradient hydrogels
Ian L Chin1, Livia Hool1,2, Yu Suk Choi1
1School of Human Sciences, The University of Western Australia, Perth, WA, Australia. yusuk.choi@uwa.edu.au.
Biomaterials Science
|September 20, 2021
Summary
Cardiac cells sense extracellular matrix (ECM) stiffness, altering cell shape and mechanomarker localization. Less mature H9C2 cells show greater sensitivity to ECM stiffness than neonatal rat cardiomyocytes (NRCMs).
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cardiovascular Research
Background:
- Extracellular matrix (ECM) remodeling is crucial in cardiac development and disease.
- Understanding cardiomyocyte mechanotransduction, how cells sense mechanical cues, is vital but limited.
- Cardiac tissue stiffness varies significantly, impacting cell behavior.
Purpose of the Study:
- To investigate stiffness-driven changes in cardiomyocyte morphology and mechanomarker expression.
- To model cardiac tissue states (necrotic, healthy, infarcted) using a continuous stiffness gradient.
- To compare mechanosensation between less mature H9C2 cells and neonatal rat cardiomyocytes (NRCMs).
Main Methods:
- Utilized linear stiffness gradient polyacrylamide hydrogels (2-33 kPa) coated with Collagen I, Fibronectin, or Laminin.
- Studied stiffness-dependent changes in cell size, shape, and nuclear size in H9C2 cells and NRCMs.
- Assessed the expression and nuclear localization of mechanomarkers (Lamin-A, YAP, MRTF-A) and cardiomyocyte structure (α-actinin).
Main Results:
- H9C2 cells exhibited mechanosensitive changes in cell size, shape, and nuclear size, along with YAP and MRTF-A nuclear translocation, across ECM coatings.
- While blebbistatin/Y27632 disrupted H9C2 cell and nuclear shape, core mechanotransduction trends persisted.
- NRCMs showed less pronounced mechanosensation, with only YAP nuclear localization increasing with stiffness; regular striations formed on Collagen I and Fibronectin but not Laminin.
Conclusions:
- ECM stiffness significantly influences cardiac cell phenotype, particularly in less mature H9C2 cells compared to NRCMs.
- Stiffness gradient hydrogels provide a valuable tool for mapping ECM-stiffness-dependent cell responses.
- Findings highlight the differential mechanosensitivity of cardiac cells based on maturity, relevant for cardiac tissue engineering and disease modeling.
