Substrate viscosity enhances correlation in epithelial sheet movement.

Area of Science:

• Biophysics
• Developmental Biology
• Tissue Engineering

Background:

• Epithelial cell movement is fundamental to tissue development, repair, and homeostasis.
• Understanding the relationship between cell-cell contact, substrate mechanics, and collective motion is crucial but remains challenging.
• Physiological substrates possess inherent viscosity, which is often not replicated in experimental models.

Purpose of the Study:

• To investigate how substrate viscoelasticity influences collective cell velocity correlations in epithelial monolayers.
• To elucidate the interplay between cell-cell interactions, extracellular matrix dynamics, and substrate properties governing epithelial tissue movement.
• To identify optimal substrate properties for mimicking physiological conditions of epithelial sheet motion.

Main Methods:

• Utilized polydimethylsiloxane (PDMS) substrates with tunable viscoelastic properties by altering cross-linking content.
• Characterized spatiotemporal correlations in cell velocity within epithelial monolayers.
• Quantified substrate viscoelasticity using the ratio of loss modulus (G'') to storage modulus (G').

Main Results:

• High spatiotemporal correlation in cell velocity was observed when the substrate's loss modulus (G'') was approximately 0.4 times its storage modulus (G').
• This optimal correlation arises from a balance between cell-cell contact forces and the adhesion/contraction of the extracellular matrix.
• When G' significantly exceeds G'', tissue contraction drives substrate flow, further increasing motion correlation.

Conclusions:

• Substrate viscoelasticity is a critical determinant of collective epithelial cell migration patterns.
• A specific balance between elastic and viscous substrate properties optimizes cell velocity correlation.
• Findings provide insights into tissue morphogenesis and offer guidance for designing biomaterials for regenerative medicine.