Gradients in cell density and shape transitions drive collective cell migration into confining environments.

Area of Science:

• Cell biology
• Biophysics
• Cancer research

Background:

• Epithelial cell collectives are crucial for development, wound healing, and tumor invasion.
• Cell migration through confined spaces presents challenges due to potential crowding and reduced migration rates.

Purpose of the Study:

• To investigate the physical transitions epithelial cells undergo when migrating through varying microchannel confinements.
• To determine the role of the breast cancer oncogene ErbB2 in modulating these migration dynamics.

Main Methods:

• Utilized a microfluidic system with contiguous microchannels of varying widths.
• Observed and analyzed the behavior of MCF10A epithelial monolayers, including cell density and shape transitions.
• Compared wild-type MCF10A cells with those overexpressing ErbB2 or constitutively active RhoA.

Main Results:

• MCF10A cells accumulated higher density and exhibited fluid-like shape changes before entering narrower channels.
• ErbB2 overexpression bypassed the need for density accumulation during migration through confinement.
• Wild-type cells showed increased migration speed in narrow channels, a sensitivity reduced by ErbB2 or active RhoA.

Conclusions:

• Collective cell migration through confinement involves density and shape transitions, akin to granular matter.
• ErbB2 oncogene alters these physical requirements for migration, potentially facilitating tumor invasion.
• Understanding these transitions offers new perspectives on tissue dynamics and disease progression.