Heterogeneity in mechanical phenotypes of cells comprising tissues as an early marker for tumorigenesis

Advances in mechanical characterization of cells have shown specific changes in mechanical properties of cells comprising healthy tissues and malignant tumors– tumor cells are softer, more deformable compared to normal tissue cells. However, this comparison is the comparison between the population means. Data shows that even in healthy tissue populations, there is a wide distribution (heterogeneity) in the mechanical properties of individual cells about the said mean. We use mechanistic computational models to study the influence of this heterogeneity on overall tissue dynamics. Our results show that increasing overall heterogeneity in cellular mechanical properties, complemented by local clustering of cells with similar mechanical phenotypes can drive the population distribution of an initially healthy tissue towards distributions representing malignant tumors. We further investigate the mobility of mechanically different cells within the heterogeneous environment to estimate a timescale over which local clustering of similar cells can occur. These results provide a theoretical estimate for the likelihood and timescale of tumor incidence in healthy tissue environments.