Spontaneous demixing of a binary cell mixture induced by self-pulsation disparity in confluent tissues

The sorting of cell mixtures is fundamental to biological processes such as embryonic development, wound healing, and cancer metastasis. Previous studies have overlooked the unique nonmotile activities of cells, such as self-pulsating. In a 2D bidisperse confluent biological tissue lacking heterogeneous tension, whether the difference in self-pulsation activity alone can drive cell spontaneous separation, remains an open question. We numerically investigated this issue using a Voronoi-based model and observed robust large-scale demixing within appropriate parameter ranges. The essence is that the self-pulsation intensity disparity leads to differences in cell rigidity, which in turn results in single selectivity at the interpenetrating interface between heterogeneous cells. As the self-pulsation intensity disparity increases, the degree of demixing first increases and then stabilizes. Moderate fluidity, self-pulsation frequency, and thermal fluctuations are also important conditions for large-scale demixing. Our study contributes to a deeper understanding of the inducing factors and core mechanisms of cell sorting in confluent tissues and provides theoretical support for subsequent experiments.