Datensatz

Zusammenfassung

Abstract
Majority of the theory on cell polarization and the understanding of cellular sensing and responsiveness to localized chemical cues has been based on the idea that non-polarized and polarized cell states can be represented by stable asymptotic switching between them. The existing model classes that describe the dynamics of signaling networks underlying polarization are formulated within the framework of autonomous systems. However these models do not simultaneously capture both, robust maintenance of polarized state longer than the signal duration, and retained responsiveness to signals with complex spatial-temporal distribution. Based on recent experimental evidence for criticality organization of biochemical networks, we challenge the current concepts and demonstrate that non-asymptotic signaling dynamics arising at criticality uniquely ensures optimal responsiveness to changing chemoattractant fields. We provide a framework to characterize non-asymptotic dynamics of system’s state trajectories through a non-autonomous treatment of the system, further emphasizing the importance of (long) transient dynamics, as well as the necessity to change the mathematical formalism when describing biological systems that operate in changing environments.

Author summary
During wound healing or embryonic development, cells in tissues or organs migrate over large distances by sensing local chemical cues. The migration response is based on cell polarization—the formation of a distinct front and back of the cell in the direction of the chemical cues. These cues are however disrupted and have a complex spatial-temporal profile. This suggests that cell polarity must be robustly established in signal direction, but also flexibly adapt when signals change. A large diversity of abstract and biochemically detailed models have been proposed to explain cell polarity, but they cannot fully describe the experimental observations. Here, we argue that cell polarization is a highly dynamic transient process, and must be studied via an explicit time-dependent form. We demonstrate that criticality organization uniquely enables formation of metastable polarized states that can be robustly maintained for a transient period even when the signals are disrupted, but also enable rapid adaptation to temporal or spatial signal changes. Using a combination of bifurcation and quasi-potential landscape analysis, we provide a framework to characterize non-asymptotic transients explicitly, and thereby further emphasize the necessity to change the mathematical formalism when describing biological systems that operate in changing environments.