Redundancy principle and the role of extreme statistics in molecular and cellular biology.

The paradigm of chemical activation rates in cellular biology has been shifted from the mean arrival time of a single particle to the mean of the first among many particles to arrive at a small activation site. The activation rate is set by extremely rare events, which have drastically different time scales from the mean times between activations, and depends on different structural parameters. This shift calls for reconsideration of physical processes used in deterministic and stochastic modeling of chemical reactions that are based on the traditional forward rate, especially for fast activation processes in living cells. Consequently, the biological activation time is not necessarily exponentially distributed. We review here the physical models, the mathematical analysis and the new paradigm of setting the scale to be the shortest time for activation that clarifies the role of population redundancy in selecting and accelerating transient cellular search processes. We provide examples in cellular transduction, gene activation, cell senescence activation or spermatozoa selection during fertilization, where the rate depends on numbers. We conclude that the statistics of the minimal time to activation set kinetic laws in biology, which can be very different from the ones associated to average times.