A subtle relationship between substrate stiffness and collective migration of cell clusters

Area of Science:

• Cell Biology
• Biophysics
• Tissue Engineering

Background:

• Physical cues from the extracellular environment regulate cell signaling.
• Single cell migration is understood, but collective cell responses to matrix stiffness are not well-established.

Purpose of the Study:

• To investigate how multicellular epithelial islands respond to varying substrate stiffness.
• To explore the mechanisms of collective cell migration and leader cell formation in response to matrix stiffness.

Main Methods:

• Patterning Madin-Darby canine kidney (MDCK) cell islands on polyacrylamide gels of tunable stiffness.
• Analyzing island expansion, cell front dynamics, focal adhesion, and actin assembly.
• Measuring force profiles along migrating epithelial structures.

Main Results:

• MDCK island expansion increased with stiffness up to an optimum, then plateaued.
• Cell front destabilization and finger-like structure formation occurred at stiffnesses above a few kPa.
• Increased stiffness led to larger focal adhesions, actin cable assembly, and more leader cells, but a decrease in global force.

Conclusions:

• Epithelial cell colonies exhibit non-trivial responses to substrate stiffness.
• Findings offer insights into morphogenesis and collective cell invasion in tumor progression.