Irvin Oppenheim Award (2022): Investigating the Functional Benefits of Criticality in Cell Sensing

The problem of understanding the function and organizing principles of biochemical circuits has attracted a lot of attention. Cells often have non-linear feedback, which can induce bifurcations, or changes in stability, in a cell’s response. These bifurcations behave very similar mathematically to thermodynamic critical points. Physicists have speculated that certain biological systems could benefit from operating close to criticality. Criticality would confer high sensitivity to external conditions, slow timescales to average dynamic fluctuations in sensory input, and facilitate coordination over large spatial scales. However, it also brings the price of large fluctuations, slow response, and a loss of spatial detail. The resolution of these trade-offs is not intuitively obvious and requires a quantitative analysis. In this talk, I will summarize our research program where we utilize a mapping from Schlogl’s second model, a well-known biochemical model exhibiting a bifurcation, onto the mean-field Ising model. This work has culminated in a study of the relevance of criticality for biochemical sensing. We find that the cell can benefit from criticality under certain conditions, but the rate at which the cell acquires information about the environment is minimized at the critical point. We discuss the application of these methods to drug response in immune cells and developmental decision in embryos.