Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification

Area of Science:

• Developmental Biology
• Cell Biology
• Biophysics

Background:

• Cellular heterogeneity in multicellular organisms contributes to variations in mechanical properties.
• These mechanical differences influence clonal population boundaries, impacting physiological outcomes like tumor progression.
• Understanding the geometry of these boundaries and their causes is crucial but challenging.

Purpose of the Study:

• To develop a pipeline for distinguishing population-boundary geometry and identifying its causes in heterogeneous tissues.
• To link specific genetic variations to distinct mechanical properties and resulting clone shapes.
• To provide a non-invasive method for studying mechanical interactions in complex tissues.

Main Methods:

• Combined multivariate analysis of clone shape with tissue mechanical simulations.
• Examined four genotypes of clones in Drosophila wing imaginal discs (wild-type, tartan overexpression, hibris overexpression, Eph RNAi).
• Quantified clone shapes using individual cell shape criteria to distinguish genetic and non-genetic heterogeneity.

Main Results:

• Identified optimal criteria for distinguishing clone shapes among different genotypes and between genetic and non-genetic heterogeneity.
• Successfully quantitatively compared experimental data with mechanical simulations.
• Determined the mechanical basis underlying the distinct clone shapes associated with each genotype.

Conclusions:

• The developed pipeline effectively links clone shape to underlying mechanical properties and genetic factors.
• This approach allows for non-invasive characterization of mechanical interactions in heterogeneous tissues.
• The findings advance the understanding of how cell mechanics influence tissue organization and physiology during development and disease.