Persistence as an Optimal Hedging Strategy.

Bacteria invest in a slow-growing subpopulation, called persisters, to ensure survival in the face of uncertainty. This hedging strategy is remarkably similar to financial hedging, where diversifying an investment portfolio protects against economic uncertainty. We provide a new, to our knowledge, theoretical foundation for understanding cellular hedging by unifying the study of biological population dynamics and the mathematics of financial risk management through optimal control theory. Motivated by the widely accepted role of volatility in the emergence of persistence, we consider several models of environmental volatility described by continuous-time stochastic processes. This allows us to study an emergent cellular hedging strategy that maximizes the expected per capita growth rate of the population. Analytical and simulation results probe the optimal persister strategy, revealing results that are consistent with experimental observations and suggest new opportunities for experimental investigation and design. Overall, we provide a new, to our knowledge, way of conceptualizing and modeling cellular decision making in volatile environments by explicitly unifying theory from mathematical biology and finance.