Utilizing multiscale engineered biomaterials to examine TGF-β-mediated myofibroblastic differentiation.

Area of Science:

• Biomaterials Science
• Cellular Mechanotransduction
• Molecular Signaling

Background:

• Cells integrate diverse mechanical and chemical signals for cellular responses.
• Interactions between extracellular matrix (ECM) properties, ligand density, and cell behavior are complex.
• Understanding how cells process combined signals in homeostasis and disease remains challenging.

Purpose of the Study:

• To develop a novel material platform for probing cell signaling responses.
• To investigate the combined effects of material viscoelasticity and transforming growth factor beta receptor (TGF-β-R) spacing on cell behavior.
• To elucidate the orthogonal contributions of mechanical cues and receptor localization to cellular outcomes.

Main Methods:

• Development of a material platform combining microgel thin films with tunable viscoelastic properties.
• Integration of DNA origami for precise control over nanoscale receptor spacing.
• Assessment of TGF-β signaling and myofibroblastic differentiation in response to varying material properties and receptor clustering.

Main Results:

• Highly viscous materials promoted increased TGF-β signaling and myofibroblastic differentiation.
• Non-fixed TGF-β-R spacing on viscous substrates enhanced cellular responses.
• Improved receptor clustering on viscous surfaces likely underlies the observed increase in signaling.

Conclusions:

• Substrate viscoelasticity and receptor localization significantly influence downstream signaling pathways.
• Cellular responses are modulated by the interplay between material properties and receptor organization.
• This platform enables future investigations into other receptor-mediated cellular processes.