Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing

Area of Science:

• Cellular biology
• Biophysics
• Collective cell migration

Background:

• Single-cell chemotaxis accuracy is limited by stochastic receptor-ligand binding.
• Genetically identical cells display varying responses to chemical signals, a factor overlooked in single-cell models.

Purpose of the Study:

• To investigate how cell-to-cell variation in signaling impacts collective chemotaxis in cell clusters.
• To determine the factors influencing the accuracy of collective cell migration in chemical gradients.

Main Methods:

• Theoretical modeling of collective cell behavior.
• Computer simulations of cell clusters responding to chemical gradients.
• Analysis of the relationship between cluster rheology and sensing accuracy.

Main Results:

• Cell-to-cell variation in signaling acts as a fundamental limitation to collective chemotaxis accuracy.
• Bias in cluster movement can exceed the effects of ligand-receptor binding noise, particularly with strongly responding cells at cluster ends.
• Cluster fluidity, influenced by cell-to-cell variation and rheology, is crucial for accurate gradient sensing.

Conclusions:

• Collective chemotaxis accuracy is significantly influenced by intercellular signaling variability.
• Optimizing cluster fluidity, even by increasing individual cell motion noise, can enhance collective gradient sensing.
• Interplay between cell-cell variation, cluster rheology, and averaging time dictates collective chemotaxis performance.