Homo-Oligomers in Signal Transduction: Modelling Approaches, Homeostasis, Ultrasensitivity, Bistability

Homo-oligomerisation of proteins is an ubiquitous phenomenon. Previous research showed that homo-dimerisation can lead to ultrasensitivity and if coupled to positive feedback, to bistability, suggesting that homo-oligomerisation plays important roles in signal transduction. This paper provides a general exploration of dynamical mathematical models of homo-oligomerisation, potential modelling pitfalls and approximative modelling strategies. Simulations and model analyses show that homo-oligomerisation on its own allows for a large variety of complex dynamic and steady-state regulatory behaviour such as short dampened oscillations or homeostatic control of monomer concentration. It furthermore can lead to bistability without feedback by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby significantly reducing the requirements previously thought necessary for the occurrence of bistability.