Feric, M. et al. Coexisting liquid phases underlie nucleolar subcompartments. Cell 165, 1686–1697 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324, 1729–1732 (2009).

Article  CAS  PubMed  Google Scholar 

Lyon, A. S., Peeples, W. B. & Rosen, M. K. A framework for understanding the functions of biomolecular condensates across scales. Nat. Rev. Mol. Cell Biol. 22, 215–235 (2021).

Article  CAS  PubMed  Google Scholar 

Alberti, S. & Dormann, D. Liquid–liquid phase separation in disease. Annu. Rev. Genet. 53, 171–194 (2019).

Article  CAS  PubMed  Google Scholar 

Alberti, S. & Hyman, A. A. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat. Rev. Mol. Cell Biol. 22, 196–213 (2021).

Article  CAS  PubMed  Google Scholar 

Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).

Article  PubMed  Google Scholar 

Martin, E. W. & Holehouse, A. S. Intrinsically disordered protein regions and phase separation: sequence determinants of assembly or lack thereof. Emerg. Top. Life Sci. 4, 307–329 (2020).

Article  CAS  PubMed  Google Scholar 

Schuster, B. S. et al. Biomolecular condensates: sequence determinants of phase separation, microstructural organization, enzymatic activity and material properties. J. Phys. Chem. B 125, 3441–3451 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borcherds, W., Bremer, A., Borgia, M. B. & Mittag, T. How do intrinsically disordered protein regions encode a driving force for liquid–liquid phase separation? Curr. Opin. Struct. Biol. 67, 41–50 (2021).

Article  CAS  PubMed  Google Scholar 

Dignon, G. L., Best, R. B. & Mittal, J. Biomolecular phase separation: from molecular driving forces to macroscopic properties. Annu. Rev. Phys. Chem. 71, 53–75 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Quiroz, F. G. & Chilkoti, A. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers. Nat. Mater. 14, 1164–1171 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dzuricky, M., Rogers, B. A., Shahid, A., Cremer, P. S. & Chilkoti, A. De novo engineering of intracellular condensates using artificial disordered proteins. Nat. Chem. 12, 814–825 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, B., Patkar, S. S. & Kiick, K. L. Application of thermoresponsive intrinsically disordered protein polymers in nanostructured and microstructured materials. Macromol. Biosci. 21, 2100129 (2021).

Article  CAS  Google Scholar 

Garcia Garcia, C., Patkar, S. S., Jovic, N., Mittal, J. & Kiick, K. L. Alteration of microstructure in biopolymeric hydrogels via compositional modification of resilin-like polypeptides. ACS Biomater. Sci. Eng. 7, 4244–4257 (2021).

Article  CAS  PubMed  Google Scholar 

Good, M. C., Zalatan, J. G. & Lim, W. A. Scaffold proteins: hubs for controlling the flow of cellular information. Science 332, 680–686 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schuster, B. S. et al. Controllable protein phase separation and modular recruitment to form responsive membraneless organelles. Nat. Commun. 9, 2985 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Simon, J. R., Eghtesadi, S. A., Dzuricky, M., You, L. & Chilkoti, A. Engineered ribonucleoprotein granules inhibit translation in protocells. Mol. Cell 75, 66–75 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nott, T. J. et al. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol. Cell 57, 936–947 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brady, J. P. et al. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation. Proc. Natl Acad. Sci. USA 114, E8194–E8203 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vernon, R. M. et al. Pi-Pi contacts are an overlooked protein feature relevant to phase separation. eLife 7, e31486 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Wang, J. et al. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174, 688–699 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murthy, A. C. et al. Molecular interactions underlying liquid–liquid phase separation of the FUS low-complexity domain. Nat. Struct. Mol. Biol. 26, 637–648 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin, E. W. et al. Valence and patterning of aromatic residues determine the phase behavior of prion-like domains. Science 367, 694–699 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schuster, B. S. et al. Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior. Proc. Natl Acad. Sci. USA 117, 11421–11431 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murthy, A. C. et al. Molecular interactions contributing to FUS SYGQ LC-RGG phase separation and co-partitioning with RNA polymerase II heptads. Nat. Struct. Mol. Biol. 28, 923–935 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bremer, A. et al. Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains. Nat. Chem. 14, 196–207 (2022).

Article  CAS  PubMed  Google Scholar 

Martin, E. W. & Mittag, T. Relationship of sequence and phase separation in protein low-complexity regions. Biochemistry 57, 2478–2487 (2018).

Article  CAS  PubMed  Google Scholar 

Tompa, P., Schad, E., Tantos, A. & Kalmar, L. Intrinsically disordered proteins: emerging interaction specialists. Curr. Opin. Struct. Biol. 35, 49–59 (2015).

Article  CAS  PubMed  Google Scholar 

Lin, Y., Currie, S. L. & Rosen, M. K. Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs. J. Biol. Chem. 292, 19110–19120 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Holehouse, A. S., Ginell, G. M., Griffith, D. & Boke, E. Clustering of aromatic residues in prion-like domains can tune the formation, state and organization of biomolecular condensates: published as part of the Biochemistry virtual special issue ‘Protein condensates’. Biochemistry 60, 3566–3581 (2021).

Article  CAS  PubMed  Google Scholar 

Fisher, R. S. & Elbaum-Garfinkle, S. Tunable multiphase dynamics of arginine and lysine liquid condensates. Nat. Commun. 11, 4628 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Devarajan, D. S. et al. Effect of charge distribution on the dynamics of polyampholytic disordered proteins. Macromolecules 55, 8987–8997 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rekhi, S. et al. Role of strong localized vs weak distributed interactions in disordered protein phase separation. J. Phys. Chem. B 127, 3829–3838 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dai, Y. et al. Programmable synthetic biomolecular condensates for cellular control. Nat. Chem. Biol. 19, 518–528 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cai, H., Vernon, R. M. & Forman-Kay, J. D. An interpretable machine-learning algorithm to predict disordered protein phase separation based on biophysical interactions. Biomolecules 12, 1131 (2022).

Article  CAS  PubMed