Cell growth rate dictates the onset of glass to fluid-like transition and long time super-diffusion in an evolving cell colony

TL;DR

This study reveals how cell growth rates influence the transition from glassy to fluid-like states and induce super-diffusive behavior in tumor cell colonies, with implications for understanding collective cell migration.

Contribution

We introduce a minimal 3D model linking cell growth to collective migration, deriving super-diffusive behavior and establishing its universality in non-equilibrium systems.

Findings

Cell growth rate affects tumor expansion and cell motility.

Cells exhibit glassy behavior at cell cycle times and super-diffusion at longer times.

Super-diffusion occurs only with an imbalance between cell birth and death rates.

Abstract

Collective migration dominates many phenomena, from cell movement in living systems to abiotic self-propelling particles. Focusing on the early stages of tumor evolution, we enunciate the principles involved in cell dynamics and highlight their implications in understanding similar behavior in seemingly unrelated soft glassy materials and possibly chemokine-induced migration of CD8$^{+}$ T cells. We performed simulations of tumor invasion using a minimal three dimensional model, accounting for cell elasticity and adhesive cell-cell interactions as well as cell birth and death to establish that cell growth rate-dependent tumor expansion results in the emergence of distinct topological niches. Cells at the periphery move with higher velocity perpendicular to the tumor boundary, while motion of interior cells is slower and isotropic. The mean square displacement, $\Delta(t)$, of cells exhibits glassy behavior at times comparable to the cell cycle time, while exhibiting super-diffusive behavior, $\Delta (t) \approx t^{\alpha}$ ($\alpha > 1$), at longer times. We derive the value of $\alpha \approx 1.33$ using a field theoretic approach based on stochastic quantization. In the process we establish the universality of super-diffusion in a class of seemingly unrelated non-equilibrium systems. Super diffusion at long times arises only if there is an imbalance between cell birth and death rates. Our findings for the collective migration, which also suggests that tumor evolution occurs in a polarized manner, are in quantitative agreement with {\it in vitro} experiments. Although set in the context of tumor invasion the findings should also hold in describing collective motion in growing cells and in active systems where creation and annihilation of particles play a role.