SELF-SIMILARITY, COLLECTIVITY, AND EVOLUTION OF FRACTAL DYNAMICS DURING RETINOID-INDUCED DIFFERENTIATION OF CANCER CELL POPULATION

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Abstract
From the reductionist perspective of molecular biology, proliferation or differentiation of eucaryotic cells is a well-defined temporal, spatial, and cell type-specific sequence of molecular cellular events. Some of those events, such as passing of the restriction point in the cell cycle, are of a stochastic nature. Results of this study indicate that, in spite of the intracellular stochasticity, cancer cells can form collective structures with fractal dimension and self-similarity. A transition from the monolayer culture to the aggregated colony facilitated interconnectedness between P19 cells, altered constitutive expression of randomly chosen retinoid-responsive genes, and increased fractal dimension of the entire population. Retinoid-induced emergence of neuron-like phenotype decreased fractal dimension significantly, slowing down dynamics of gene expression. Since the differentiated P19 cells retained both their cancer phenotype and a number of gene defects, we conclude that the appropriate dynamics of intracellular events is neccessary for the proper course of differentiation. Owing to self-similarity, dynamics of cellular expansion can be measured by a fractal dimension in a single cell or in the entire population.