Scale-free aggregation and interface fluctuations of cancer clusters in cancer-endothelial cell mixtures: From the dilute state to confluent monolayer

Abstract

We experimentally investigate the multiscale dynamical and scaling behaviors of the morphology, motion, and area distribution of segregated cancer clusters of proliferating cancer-endothelial cell mixtures, from the initial randomly distributed dilute state to the jammed confluent monolayer state. Cancer cells (CCs) have higher motilities than endothelial cells (ECs) and weaker CC-EC and CC-CC cohesive couplings than EC-EC coupling. It is found that, with increasing waiting time t_{w}, CCs proliferate, move, and aggregate into clusters with fractal cluster boundaries, increasing averaged cluster area, and the gradual transition to the self-similar power-law distribution of single cluster areas. In CC clusters, multiscale turbulentlike motion and the interaction with surrounding ECs are the keys for self-similar multiscale spatial fluctuations of the velocities and fractal structure of CC cluster boundaries. The larger CC cluster allows stronger longer-length fluctuations. It causes the increasing fractal dimension and scaling exponents of the relative motion of CC cluster boundaries, which can be suppressed by proliferation-induced crowding and dynamical slowing down.