Self-similarity, collectivity, and evolution of fractal dynamics during retinoid-induced differentiation of cancer cell population

From the reductionist perspective of molecular biology, proliferation or di fferentiation of eucaryotic cells is a well-defined temporal, spatial, and cell type-specific sequence of molecular cellular events. Some of those eve nts, such as passing of the restriction point in the cell cycle, are of a s tochastic nature. Results of this study indicate that, in spite of the intr acellular stochasticity, cancer cells can form collective structures with f ractal dimension and self-similarity. A transition from the monolayer cultu re to the aggregated colony facilitated interconnectedness between P19 cell s, altered constitutive expression of randomly chosen retinoid-responsive g enes, and increased fractal dimension of the entire population. Retinoid-in duced emergence of neuron-like phenotype decreased fractal dimension signif icantly, slowing down dynamics of gene expression. Since the differentiated P19 cells retained both their cancer phenotype and a number of gene defect s, we conclude that the appropriate dynamics of intracellular events is nec cessary 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.