ArticleProceedings of the National Academy of Sciences of the United States of America2021
Physical theory of biological noise buffering by multicomponent phase separation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 91 citations in OpenAlex.
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- Rules of selective condensation in cells.Nature chemistry · 2024Article
- Physical limits to acceleration of enzymatic reactions inside phase-separated compartments.Physical review. E · 2024Article
- MolPhase, an advanced prediction algorithm for protein phase separation.The EMBO journal · 2024Article
- GENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems.Nature communications · 2024Article
- Mitigating transcription noise via protein sharing in syncytial cells.Biophysical journal · 2024Article
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2 authors at 1 institution in 1 country.
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Abstract
Maintaining homeostasis is a fundamental characteristic of living systems. In cells, this is contributed to by the assembly of biochemically distinct organelles, many of which are not membrane bound but form by the physical process of liquid-liquid phase separation (LLPS). By analogy with LLPS in binary solutions, cellular LLPS was hypothesized to contribute to homeostasis by facilitating "concentration buffering," which renders the local protein concentration within the organelle robust to global variations in the average cellular concentration (e.g., due to expression noise). Interestingly, concentration buffering was experimentally measured in vivo in a simple organelle with a single solute, while it was observed not to be obeyed in one with several solutes. Here, we formulate theoretically and solve analytically a physical model of LLPS in a ternary solution of two solutes (ϕ and ψ) that interact both homotypically (ϕ-ϕ attractions) and heterotypically (ϕ-ψ attractions). Our physical theory predicts how the coexisting concentrations in LLPS are related to expression noise and thus, generalizes the concept of concentration buffering to multicomponent systems. This allows us to reconcile the seemingly contradictory experimental observations. Furthermore, we predict that incremental changes of the homotypic and heterotypic interactions among the molecules that undergo LLPS, such as those that are caused by mutations in the genes encoding the proteins, may increase the efficiency of concentration buffering of a given system. Thus, we hypothesize that evolution may optimize concentration buffering as an efficient mechanism to maintain LLPS homeostasis and suggest experimental approaches to test this in different systems.
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