Noise-induced survival resonances during fractional killing of cell populations

TL;DR

This paper investigates how stochastic effects and environmental periodicity influence fractional killing in cell populations, revealing phase transitions and survival resonance phenomena that affect drug treatment outcomes.

Contribution

It introduces a stochastic population model with age-dependent rates to quantitatively analyze fractional killing and uncovers novel survival resonance effects in periodic drug environments.

Findings

Increasing cell cycle noise causes a phase transition from complete to fractional killing.

Increasing death noise can reverse the phase transition.

Periodic environments induce survival resonance peaks at specific times.

Abstract

Fractional killing in response to drugs is a hallmark of non-genetic cellular heterogeneity. Yet how individual lineages evade drug treatment, as observed in bacteria and cancer cells, is not quantitatively understood. We analyse a stochastic population model with age-dependent division and death rates and characterise the emergence of fractional killing as a stochastic phenomenon under constant and periodic drug environments. In constant environments, increasing cell cycle noise induces a phase transition from complete to fractional killing, while increasing death noise can induce the reverse transition. In periodic drug environments, we discover survival resonance phenomena that give rise to peaks in the survival probabilities at division or death times that are multiples of the environment duration not seen in unstructured populations.