Stress distributions and cell flows in a growing cell aggregate

Area of Science:

• Biophysics
• Cell Biology
• Tissue Engineering

Background:

• Multicellular spheroids are used as models for solid tumors and developing tissues.
• Understanding spheroid mechanical responses to external stimuli is crucial for predicting tissue behavior.
• Cellular processes like division and apoptosis are influenced by mechanical forces.

Purpose of the Study:

• To investigate the short-time mechanical response of multicellular spheroids to external pressure jumps.
• To develop a theoretical model explaining observed cell density changes.
• To estimate the isotropic compression modulus of spheroid tissue.

Main Methods:

• Experimental application of external pressure jumps to multicellular spheroids.
• Microscopic observation of cell density changes over time.
• Development of a theoretical framework for polarized spheroids considering stress-dependent cell dynamics.
• Comparison of theoretical predictions with experimental data.

Main Results:

• Cell density increased in the spheroid center within 5 minutes of a pressure jump, while the surface density remained unchanged.
• Experimental observations were explained by assuming radial cell polarization.
• The developed theory predicted a power-law decay of short-time cell density increase from the spheroid center.
• Good agreement was found between the theoretical model and experimental results.

Conclusions:

• Cell polarization is a key factor in the short-time mechanical response of multicellular spheroids to pressure changes.
• The developed theory provides a framework for understanding stress-induced tissue remodeling.
• The study successfully estimated the isotropic compression modulus of the spheroid tissue through model-experiment comparison.