RAB5A Promotes Active Fluid Wetting by Reprogramming Breast Cancer Spheroid Mechanics.

Area of Science:

• Biophysics
• Cell Biology
• Cancer Research

Background:

• Unjamming transitions, from solid-like to fluid-like states, are crucial for breast epithelial cancer invasion.
• The mechanical interplay between phase and dimension transitions, like wetting, is critical for metastatic dissemination but remains poorly understood.

Purpose of the Study:

• To investigate how unjamming transitions, mediated by RAB5A GTPase, affect carcinoma spheroid mechanics.
• To elucidate the role of active wetting as a novel mode of tumor expansion.
• To understand the molecular and biophysical mechanisms underlying solid tumor invasion.

Main Methods:

• Studied carcinoma spheroid fluidity, rigidity, and adhesion mechanics.
• Analyzed integrin subunit expression and focal adhesion dynamics.
• Utilized nanomechanical mapping, Brillouin microscopy, and 2.5D traction force analysis.

Main Results:

• Unjamming, via RAB5A GTPase, drives supracellular active wetting, a new mode of tumor expansion.
• Spheroid fluidification enhances integrin expression and focal adhesion dynamics, leading to fluid-like spreading.
• Fluidized spheroids form cohesive
• supracells
• with a stiff peripheral actin bundle and exhibit cell softening in the core, mimicking liquid droplet wetting.

Conclusions:

• Unjamming-driven active wetting is a key mechanism in solid tumor invasion.
• Nanoscale integrin clustering regulates collective-scale phase transitions during wetting.
• This study provides a framework for understanding the molecular and biophysical underpinnings of cancer cell invasion and metastasis.