Extracellular matrix plasticity as a driver of cell spreading

Area of Science:

• Biophysics
• Materials Science
• Cell Biology

Background:

• Cell morphology and behavior are influenced by the viscoelastic properties of adhesion substrates.
• Existing biomaterials often couple plastic deformation, degradation, and stress relaxation, hindering the study of individual variables.
• Understanding substrate mechanics is crucial for processes like wound repair and embryonic development.

Purpose of the Study:

• To decouple irreversible creep from stress relaxation and modulus in a nondegradable polymer architecture.
• To investigate the independent role of network plasticity in controlling mesenchymal stem cell spreading.
• To elucidate the relationship between extracellular matrix (ECM) plasticity and cell behavior.

Main Methods:

• Development of a novel nondegradable polymer system to isolate matrix plasticity.
• Experimental assessment of mesenchymal stem cell spreading on substrates with varying plasticity.
• Kinetic Monte Carlo simulations to model cell spreading dynamics.
• Analysis of ECM adhesion and remodeling gene expression.

Main Results:

• Network plasticity was shown to independently control mesenchymal stem cell spreading.
• A biphasic relationship between plasticity and cell spreading, dependent on cell-intrinsic forces, was identified.
• Inhibiting actomyosin contractility shifted the plasticity-dependent cell spreading relationship.
• Simulations strongly correlated with experimental data regarding ECM plasticity's effect on cell spreading.
• Matrix plasticity was found to regulate key ECM adhesion and remodeling genes.

Conclusions:

• Matrix plasticity plays a critical, independent role in regulating stem cell biophysics, particularly cell spreading.
• The findings provide a mechanistic understanding of how substrate plasticity influences cell behavior.
• This research has significant implications for the rational design of biomaterials for enhanced stem cell-based therapeutics.