Cell-state organization by exploratory sloppy dynamics

Abstract Cell-state organization, manifested in metabolism, morphology, and functionality of the cell, is of a dual nature; highly stable even under fluctuating conditions on the one hand, and flexible to adapt to novel conditions on the other hand. Here, based on our experiments studying the adaptation of yeast cells to an unforeseen challenge, we discuss the organization principles enabling the emergence of order, the stabilization of a cell state, given this duality. We propose that a cell state emerges by self-organized exploratory dynamics. We further discuss the barriers toward a physical framework for cell-state organization, our inability to reverse engineer living systems, and the difficulties in identifying the underlying relevant degrees of freedom. We finally hypothesize that the living cell is a sloppy dynamical system, in which the dynamics are largely insensitive to the kinetics of its interacting molecules. Therefore, a physical picture of cell-state organization should go beyond the framework of prestructured networks of interactions, and treat the evolving intracellular interactions as part of the self-organization dynamics. These dynamics reflect coupling of the cell’s internal processes with the environment and integration over its physiological as well as evolutionary histories.