Samanta, H. S. | bioRxiv Science

bioRxiv2020

Far from equilibrium dynamics of tracer particles embedded in a growing multicellular spheroid

Local stresses on the cancer cells (CCs) have been measured by embedding inert tracer particles (TPs) in a growing multicellular spheroid. The utility of the experiments requires that the TPs do not alter the CC microenvironment. We show, using theory and extensive simulations, that proliferation and apoptosis of the CCs, drive the dynamics of the TPs far from equilibrium. On times less than the CC division times, the TPs exhibit sub-diffusive behavior (the mean square displacement, [Formula] with {beta}TP < 1). Surprisingly, in the long-time limit, the motion of the TPs is hyper-diffusive ([Formula] with TP > 2) due to persistent directed motion for a number of CC division times. In contrast, CC proliferation randomizes their motion resulting from jamming at short times to super-diffusive behavior, with CC exceeding unity, at long times. Surprisingly, the effect of the TPs on CC dynamics and radial pressure is negligible, suggesting that the TPs are reliable reporters of the CC microenvironment.

biophysics↗

bioRxiv2017

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

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 ( > 1), at longer times. We derive the value of {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 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.

biophysics↗