Tipping the Balance: a criticality perspective

TL;DR

This paper models tumor cell heterogeneity using a stochastic framework, revealing how environmental noise and coupling influence the dominance of cell subpopulations and identifying critical transition signatures.

Contribution

It introduces a stochastic model linking phenotypic heterogeneity in tumors to environmental noise and coupling, highlighting phase transition analogies and transition signatures.

Findings

Phase diagram of tumor cell subpopulations under noise and coupling.

Transition from balanced to dominant subpopulations at critical coupling.

Variance and entropy measures signal the transition point.

Abstract

Cell populations are often characterised by phenotypic heterogeneity in the form of two distinct subpopulations. We consider a model of tumour cells consisting of two subpopulations: non-cancer promoting (NCP) and cancer-promoting (CP). Under steady state conditions, the model has similarities with a well-known model of population genetics which exhibits a purely noise-induced transition from unimodality to bimodality at a critical value of the noise intensity $\sigma^2$. The noise is associated with a parameter $\lambda$ representing the system-environment coupling. In the case of the tumour model, $\lambda$ has a natural interpretation in terms of the tissue microenvironment which has considerable influence on the phenotypic composition of the tumour. Oncogenic transformations give rise to considerable fluctuations in the parameter. We compute the $\lambda-\sigma^2$ phase diagram in a stochastic setting, drawing analogies between bifurcations and phase transitions. In the region of bimodality, a transition from a state of balance to a state of dominance, in terms of the competing subpopulations, occurs at $\lambda=0$. Away from this point, the NCP (CP) subpopulation becomes dominant as $\lambda$ changes towards positive (negative) values. The variance of the steady state probability density function as well as two entropic measures provide characteristic signatures at the transtion point.