The interplay between phase separation and self-assembly is an instriguing topic that has important implications in different fields, ranging from statistical mechanics to materials science and biology. Recent advances in cell biology have shown that such an interplay underlies the formation, dissolution and function of a new class of organelles called "membraneless organelles". These are compartmentalized portions of the cell that act as chemical reactors and whose formation and function is dynamically regulated by the cellular environment and signalling machinery. In this project we take inspiration from recent advances in the cell biology to develop a model that can mimic, on a qualitative level, the thermodynamics and kinetics of formation of membraneless organelles. To this regard we will employ numerical simulations of coarse-grained models to address (i) the kinetics of formation and dissolution of membraneless organelles modelled as phase-separated condensates formed by protein-like particles and (ii) the static and dynamic properties of membraneless organelles in the presence of client (host) molecules of different type. Our results will be relevant not only for the biophysics of the cell, but they will also contribute to a deeper understanding of the complex relationship between phase separation and self-assembly.
The cell homeostasis is a delicate equilibrium that hinges on the subtle interplay between the external environment, the internal cellular state and the role the cell has to fulfil. Any advancements on the understanding of how the cell copes with changes of the environment is thus of great importance. The recent discovery that membraneless organelles, always present in some form in the cellular steady state, can dynamically respond to external and internal changes (e.g. stress build-up, altered conditions, alterations in the cellular signalling) needs to be completed by a deep understanding of their function and of the mechanisms that underlie their formation and dissolution. Here we plan to provide a physical insight on the latter, advancing the field by understanding the role of the microscopic interactions between the organelle constituents. Building on the work done in the past fifteen years by the proponents, we will develop a coarse-grained model that can act as a framework and be extended to incorporate additional complexity (such as the presence of RNA or specific RNA-binding proteins that are important in some specific membraneless organelles[14]). As such, the results of the projects will be not only useful on their own, but can also seen as solid starting points to build up more complex descriptions that will bridge the gap between the microscopic knowledge of the structure of the building blocks and their mesoscopic behaviour.
In addition to the importance for the biology of the cell, our results will also be important from a fundamental point of view. Indeed, the relationship between phase separation and self-assembly is an important topic in soft matter in particular and in statistical mechanic in general, and hence a model specifically tailored to tackle this issue will provide new opportunities to the field[2].
Finally, synthetic building blocks that mimic the specificity of biomacromolecules (or directly incorporate them) are increasingly being used to build proof-of-concept materials with target properties[7]. As a consequence, the results derived here for in vivo systems may be translated and extended to the case of synthetic materials, bridging together biophysics, soft matter and materials science.
REFERENCES (see also "Descrizione obiettivi progetto" and "Inquadramento della ricerca"):
[14] A. Jain, R. D. Vale, Nature 546, 243 (2017)