The “friend and foe” of deterministic and stochastic cell-cell variations

Abstract By diversifying, cells in a clonal population can together overcome the limits of individuals. Diversity in single-cell growth rates allows the population to survive environmental stresses, such as antibiotics, and grow faster than undiversified population. These functional cell-cell variations can arise stochastically, from noise in biochemical reactions, or deterministically, by asymmetrically distributing damaged components. While each of the mechanism is well understood, the effect of the combined mechanisms is unclear. To evaluate the contribution of the deterministic component we mapped the growing population to the Ising model. Model results, confirmed by simulations and experimental data, show that cell-cell variations increase near-linearly with stress. As a consequence, we predict that the entropic gain — the gain in population doubling time compared to an “average” cell — is primarily stochastic at low stress but crosses over to deterministic at higher stresses. Furthermore, we find that while the deterministic component minimizes population damage, stochastic variations antagonize this effect. Together our results may help identifying stress-tolerant pathogenic cells and thus inspire novel antibiotic strategies.