Structural adaptation and robustness of Dictyostelium ligand-receptor kinetics for low and high ligand concentrations

Ligand receptor interactions are responsible for adaptation and robustness of all cellular life to most chemical external stimuli, and are mediated by cellular networks whose structure appears to be highly conserved among different organisms. Although many ligand receptor networks exhibit a common structure, the dynamic response to variations in the ligand concentration can be vastly different from network to network. This suggests that certain parameters of the network have evolved by nature to provide appropriate performance and robustness characteristics for different situations. We investigate the system's response in the cases of low and and high concentrations of external cAMP, corresponding to two distinct stages of the Dictyostelium life cycle. Our analysis reveals highly robust responses from the ligand-bound receptor kinetics for low ligand concentration, and such high levels of robustness are likely to be required from each individual Dictyostelium cell to survive this stage of its life cycle. We show that overshoot is prohibited by the structure of network regardless of the kinetic constants values, and the particular values chosen in the original model are shown to lead to a critically damped response. On the other hand, for high ligand concentrations an extreme reduction in the magnitude of the network response to external signals is observed, and this may be responsible for the completely different physiological behaviour of the organism as groups of up to 10(5) Dictyostelium cells aggregate to form a slug. The receptor ligand interaction networks may have evolved to provide an optimal trade-off between maximizing the speed of response and prohibiting overshoot as it follows external oscillatory signals. Copyright (C) 2010 John Wiley & Sons, Ltd.