Liquid-liquid phase separation as an organizing principle of intracellular space: overview of the evolution of the cell compartmentalization concept

At the turn of the twenty-first century, fundamental changes took place in the understanding of the structure and function of proteins and then in the appreciation of the intracellular space organization. A rather mechanistic model of the organization of living matter, where the function of proteins is determined by their rigid globular structure, and the intracellular processes occur in rigidly determined compartments, was replaced by an idea that highly dynamic and multifunctional soft matter lies at the heart of all living things. According this new view, the most important role in the spatio-temporal organization of the intracellular space is played by liquid-liquid phase transitions of biopolymers. These self-organizing cellular compartments are open dynamic systems existing at the edge of chaos. They are characterized by the exceptional structural and compositional dynamics, and their multicomponent nature and polyfunctionality provide means for the finely tuned regulation of various intracellular processes. Changes in the external conditions can cause a disruption of the biogenesis of these cellular bodies leading to the irreversible aggregation of their constituent proteins, followed by the transition to a gel-like state and the emergence of amyloid fibrils. This work represents a historical overview of changes in our understanding of the intracellular space compartmentalization. It also reflects methodological breakthroughs that led to a change in paradigms in this area of science and discusses modern ideas about the organization of the intracellular space. It is emphasized here that the membrane-less organelles have to combine a certain resistance to the changes in their environment and, at the same time, show high sensitivity to the external signals, which ensures the normal functioning of the cell.

Automated summary

Fundamental changes took place in the understanding of protein structure and function, as well as the organization of intracellular space, at the turn of the twenty-first century. The traditional mechanistic model was replaced by the idea of dynamic and multifunctional soft matter playing a central role. Liquid-liquid phase transitions of biopolymers were identified as crucial for spatio-temporal organization. Changes in external conditions could disrupt cellular bodies' formation and lead to the emergence of amyloid fibrils.