Interactions among the multitude of macromolecules populating the cytoplasm can lead to the emergence of coexisting phases formed via phase separation. This phenomenon plays a crucial role in the spatial organization of cells and the regulation of their functions. Many of the molecules that drive phase separation can undergo transitions among different states. Proteins, for example, can go through conformational transitions and switch among different phosphorylation states. In addition, proteins that are relevant for phase separation can assemble into oligomers of different sizes. Both molecular transitions and oligomerization can be described as chemical reactions in the context of theories that account for phase separation in multicomponent mixtures. In this work, we discuss how chemical reactions can be used to control coexisting phase composition and shape. In particular, focusing on molecular transitions among two states of a protein, we find a discontinuous thermodynamic phase transition in the composition of the protein-dense phase, as a function of temperature. Breaking detailed balance of the molecular transition by continuous fuel addition can also be used to control the number of distinct coexisting phases and their composition. Additionally, fuel turnover can lead to the emergence of novel patterns as the system approaches a non-equilibrium stationary state. We focus on the mechanism that leads to the formation of ring-like patterns, motivated by the observation of similar shapes in experiments with chemical reaction cycles coupled to a fuel reservoir. We propose that, due to chemical reactions, the composition at the centre of the dense phase can be altered, leading to an instability that drives the formation of a new interface.
Controlling the composition of coexisting phases becomes crucial when the number of components and the number of reactions among them rises. This is the case in mixtures containing proteins that can be found in a monomeric state but also form aggregates of arbitrary size. We characterise the equilibrium of such systems in the limit of maximum aggregate size going to infinity. For systems that phase separate, we show that the aggregate size distribution can be different in each of the coexisting phases and is determined by the temperature and the energy of bonds between monomers. Mixtures composed of disk-like or spherical aggregates can undergo a gelation transition. Gelation can be considered as a special case of phase coexistence between a dilute phase (the 'sol') containing aggregates of finite size, and a 'gel' phase, corresponding to an aggregate of infinite size. Lowering the temperature leads to a transition from two coexisting ''sol' phases to the coexistence of a 'sol' phase and a ''gel'' phase. In summary, this work provides a theoretical framework to study phase-separating systems composed of many components that undergo chemical reactions. Furthermore, we discuss how to exploit such reactions to control the composition of coexisting phases.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86555 |
| Date | 25 July 2023 |
| Creators | Bartolucci, Giacomo |
| Contributors | Weber, Christoph A., Jülicher, Frank, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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