On the origin of universal cell shape variability in confluent epithelial monolayers

Area of Science:

• Cell biology
• Biophysics
• Mathematical modeling

Background:

• Cell shape is crucial for biological functions like cell fate and division.
• Cell-to-cell shape variability is often dismissed as noise.
• Recent studies show epithelial monolayers exhibit a nearly universal shape distribution.

Purpose of the Study:

• To develop a theoretical framework explaining the universal distribution of cell shape variability.
• To identify the underlying physical principles governing cell shape in epithelial monolayers.
• To provide a unified method for analyzing and comparing diverse epithelial systems.

Main Methods:

• Developed a mean-field analytical theory for cell shape variability, focusing on contractility and adhesion.
• Characterized cell shape using aspect ratio (r).
• Derived a probability distribution function (PDF) for r governed by a single parameter (α).

Main Results:

• Identified a universal relationship between the standard deviation and average of cell aspect ratio (r).
• The scaled aspect ratio PDF is nearly universal, governed by parameter α.
• Derived a scaled area distribution described by parameter μ.
• Demonstrated that average cell shape dictates both variability and dynamics in confluent monolayers.
• Validated the theory using simulations and experimental data.

Conclusions:

• Cell shape distribution in epithelial monolayers is an inevitable consequence of underlying mathematical properties.
• Parameters α and μ can differentiate the effects of physical conditions (e.g., maturation) on system properties.
• The developed framework offers a unified approach to analyze cell shape statics and dynamics across diverse epithelial systems, applicable even in the fluid regime.