Principles governing where cells tolerate cell-to-cell variability

Determine the principles and mechanisms by which cells decide where to tolerate extrinsic cell-to-cell variability across kinetic parameters of transcription and other cellular processes, and characterize how this allocation of variability shapes entropy production and irreversibility at the population level.

Background

The paper develops an analytic framework to assess how extrinsic variability in kinetic parameters affects the entropy production rate of transcription across a population. It shows that variability can either amplify or suppress irreversibility depending on which parameter varies, implying that the placement of extrinsic noise is consequential for population-level dynamics.

Building on connections to information-theoretic limits on noise suppression, the authors argue that evolutionary pressures may not only shape intrinsic stochasticity but also where extrinsic heterogeneity is tolerated or constrained. This motivates an explicit open problem: elucidating the decision principles cells use to distribute and manage cell-to-cell variability.