Cyclic stretching combined with cell-cell adhesion is sufficient for inducing cell intercalation

Area of Science:

• Cell Biology
• Biophysics
• Developmental Biology

Background:

• Cell intercalation is crucial for morphogenesis but its mechanisms are unclear.
• Understanding how mechanical forces influence collective cell behavior is essential.

Purpose of the Study:

• To investigate the role of cyclic stretching in inducing cell intercalation.
• To elucidate the molecular mechanisms underlying stretch-induced cell intercalation.

Main Methods:

• Epithelial cells were cultured on micropatterned substrates and subjected to synchronized cyclic stretching.
• Synchronized imaging and mathematical modeling were employed.
• Small-molecule inhibitors targeting myosin II and Wnt signaling were used.

Main Results:

• Uniaxial cyclic stretching induced cell intercalation, cell shape change, and remodeling of cell-cell interfaces.
• Mathematical modeling indicated cell shape change and dynamic adhesions suffice for intercalation.
• Myosin II activity is required for stretch-induced intercalation and vertex orientation.
• Wnt signaling is essential for intercalation and vertex resolution but not initial shape change.

Conclusions:

• Cyclic stretching can induce cell intercalation through mechanical forces, cell shape changes, and dynamic adhesions.
• Myosin II and Wnt signaling play distinct, crucial roles in this process.
• This study provides insights into the mechanical regulation of collective cell migration and tissue development.