Cyclic Stiffness Modulation of Cell-Laden Protein-Polymer Hydrogels in Response to User-Specified Stimuli including...

Area of Science:

• Biomaterials Science
• Mechanobiology
• Cellular Physiology

Background:

• Extracellular matrix mechanical signals regulate cell functions.
• The impact of dynamic and heterogeneous mechanical cues is not well understood.

Purpose of the Study:

• To create novel protein-polymer hydrogels with tunable stiffness.
• To investigate the role of cyclic mechanical loading in cell transdifferentiation.

Main Methods:

• Developed a modular semisynthetic approach using dual-chemoenzymatic modification.
• Created fusion protein-based hydrogel crosslinkers with stimuli-dependent association (calmodulin for calcium sensitivity, LOV2 for light sensitivity).
• Utilized these moduli-switchable hydrogels to study fibroblast-to-myofibroblast transdifferentiation in 3D cell cultures.

Main Results:

• Successfully synthesized protein-polymer hydrogels with reversible stiffening in response to calcium or light.
• Demonstrated spatiotemporal control over material properties around living cells.
• Showed that cyclic mechanical loading significantly influences fibroblast-to-myofibroblast transdifferentiation in 3D.

Conclusions:

• The developed moduli-switchable hydrogels offer a new tool for mechanobiology research.
• These materials enable precise investigation of matrix-driven cell behavior.
• Provides new avenues to probe and direct cell physiology in 4D.