Are phases an appropriate description for cells? – Fluctuation dominated regime in finite systems with many components

Phase separation has emerged as an important topic for cellular function. From lipid rafts to liquid-liquid phase separation, our current understanding is that it is crucial for organization. We putatively expect that rules extracted from simple systems, two component mixtures, extend to multicomponent systems. While this is true in the thermodynamic limit, I will discuss here the thermodynamic limit for multicomponent systems. Using a toy model, I will show that what we consider "large systems" is largely subjective and dependent on details in multicomponent systems. For "small" systems, rules are very different, and the system is dominated by fluctuations. Usual assumptions, such as equivalence of thermodynamic ensembles, are broken. Still, the system can be driven to exhibit behavior that is similar to a phase transition, for instance by changing the statistical ensemble. Practically, this means that observed phase behavior may be largely dependent on system preparation. The typical signature of this regime is eerily similar to many observations in cells. This naturally leads to a fundamental question: is the traditional phase behavior an appropriate description for cellular behavior?