ReviewARticlehttps://doi.org/10.1038/s41587-019-0341-61DepartmentofChemicalandBiologicalEngineering,PrincetonUniversity,Princeton,NJ,USA.2HowardHughesMedicalInstitute,DepartmentofChemicalandBiologicalEngineering,PrincetonUniversity,Princeton,NJ,USA.3Theseauthorscontributedequally:DanBracha,MackenzieT.Walls.*e-mail:cbrangwy@princeton.eduAcentralfeatureofbiologicalsystemsiscompartmental-izationacrossdiverselengthscales—fromorganstosub-micronintracellularorganelles.Justastissue-engineeredorgansholdgreatpromiseforhumanhealth,effortstowardrepro-graming,mendingorcreatingintracellularcompartmentsthroughorganelleengineeringhavethepotentialtofundamentallychangeourabilitytomodulatephysiologicalprocesses.Thebest-knownorganellesaremembrane-boundstructures,butcellsalsocontainmanyorganelleswithoutmembranesthathavediversebiologicalfunctions.However,untilrecently,boththeprinciplesunderly-ingtheassemblyofmembrane-lessorganellesandtheirbiophysi-calpropertieshavebeenlargelyunknown,hinderingourabilitytorationallydesignandexploitthemforbiotechnologicalpurposes.Overthelastdecade,ourunderstandingofthesestructureshasadvancedrapidly,beginningwiththediscoverythatmembrane-lessorganellesknownasPgranulesassemblethroughthecondensationofvariousproteinsandRNAsintoliquiddroplets1.Thisprocess,knownasliquid–liquidphaseseparation(LLPS),hassincebeenimplicatedintheassemblyofdozensofmembrane-lessstructures,increasinglyreferredtoascondensates,whereitplaysacentralroleinthediversestructuralandfunctionalpropertiestheyexhibit(Fig.1)2,3.Forinstance,coalescenceofnucleoli4,reversibleassemblyandbio-moleculesequestrationofstressgranules5andgenomeorganizationbyenhancerclustersandheterochromatin6–10areallthoughttoarisefromLLPS,whichyieldsmalleableanddynamicliquid-likestruc-turesthatfacilitatevariousbiologicalfunctions.However,nativecondensatesarefarfromsimpleliquids;mixedbiomolecularinter-actionmodesandrichcompositionalheterogeneitywithinthenon-equilibriumintracellularenvironmentyieldcomplexviscoelasticstructu...
