ライフサイエンスコーパス: LLPS

1 LLPS does, however, greatly accelerate formation of fibr

2 LLPS increases the specific activity of actin regulatory

3 LLPS of AfrLEA6 is driven by the SMP domain, while the s

4 LLPS was achieved by deliquescing and then drying the pa

5 LLPS was shown to facilitate tau amyloid aggregation in

6 LLPS-driven aggregation may be a common amyloid feature

7 tion D169G impairs the NEAT1-mediated TDP-43 LLPS and NB assembly, causing excessive cytoplasmic tran

8 entrations indirectly promoted SH3(5)-PRM(5) LLPS, by taking up volume in the bulk phase and thereby

9 Among LLPS-prone proteins, TAR DNA-binding protein of 43 kD (T

10 Because chromatin compaction and LLPS are collective phenomena, linking their modulation

11 the relationship between stress granules and LLPS, for example, in the context of protein disorder, s

12 tionship between the aggregation process and LLPS remains largely unknown.

13 reened out to block SARS2-NP SUMOylation and LLPS, and consequently inhibit SARS-CoV-2 replication an

14 e functional roles of chromatin topology and LLPS in regulating gene expression remain poorly underst

15 As LLPS introduces another layer of complexity into fibrill

16 As LLPS-competent molecules are frequently implicated in di

17 SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity.

18 We show that this increase occurs because LLPS of the Nephrin-Nck-N-WASP signaling pathway on lipi

19 A link may exist between LLPS of proteins and the disease-related process of amyl

20 ng that there might be a strong link between LLPS and the pathogenic process in these disorders.

21 ns and further ramifications of biomolecular LLPS at low temperatures and high hydrostatic pressures

22 ular interactions that underpin biomolecular LLPS have been of increased interest due to the importan

23 The measurements of both LLPS temperature and PEG partitioning in the ternary gam

24 These results were observed both in bulk LLPS and in lipid-stabilized, phase-separated aqueous mi

25 rovide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.

26 logy with LLPS in binary solutions, cellular LLPS was hypothesized to contribute to homeostasis by fa

27 ted by tau-RNA/heparin complex coacervation (LLPS-ED).

28 ven LLPS induced by high salt concentration (LLPS-HS), and compare it to electrostatically driven LLP

29 molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA con

30 nteractions in amino acid sequence-dependent LLPS.

31 g that the RtoK mutant has a much diminished LLPS propensity.

32 l-intrinsic restriction factor that disrupts LLPS to limit viral replication and spread.

33 entrations that are usually used to dissolve LLPS droplets (5-10%), both kinases and phosphatases wer

34 rated an integrated model that distinguished LLPS-prone sequences both from structured proteins and f

35 sically disordered regions (IDRs) that drive LLPS and constitute a new class of phase separating elem

36 -mimetic mutant appeared sufficient to drive LLPS.

37 , and compare it to electrostatically driven LLPS represented by tau-RNA/heparin complex coacervation

38 on a model system of hydrophobically driven LLPS induced by high salt concentration (LLPS-HS), and c

39 he microtubule binding domain (MTBD), drives LLPS and does so under the control of its phosphorylatio

40 However, dysregulated LLPS can also facilitate aberrant phase transitions and

41 ticomponent interactions dominate endogenous LLPS, and give rise to nucleoli and other condensates th

42 ntration is a defining feature of endogenous LLPS(7-9), and has been suggested as a mechanism for int

43 verall, we outline the framework to evaluate LLPS in vivo in bacteria, we describe the bacterial syst

44 All but one of 12 variants exhibited LLPS, albeit to different extents, despite substantial d

45 ng of biomacromolecular complexes exhibiting LLPS ability.

46 stently accounted for available experimental LLPS data on the wild-type, a charge-scrambled, a phenyl

47 Although FRQ phosphorylation favors LLPS, LLPS feeds back to reduce FRQ phosphorylation by C

48 ity of scaffolds (biomolecules essential for LLPS) dominates the phase landscape, introduction of cli

49 This work provides direct evidence for LLPS in bacteria and demonstrates that this process can

50 nderlie the thermodynamic driving forces for LLPS, forming condensates that can facilitate the assemb

51 G3BP1 regulates its intrinsic propensity for LLPS, and this is fine-tuned by phosphorylation within t

52 to alternate scaffold sites not required for LLPS or that have higher-than-scaffold valencies form ad

53 Importantly, while not required for LLPS, fibrillization is enhanced in protein-rich droplet

54 , both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology.

55 1, underscoring that, to a degree, important LLPS-driving pai-related interactions are embodied in cl

56 es, which may originate from disturbances in LLPS and membraneless organelles.

57 recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation.

58 ggregation-prone and aggregation-independent LLPS.

59 epending on context, bis-ANS can both induce LLPS de novo as well as prevent formation of homotypic l

60 Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that co

61 (Y122A) that exhibits defective cAMP-induced LLPS, we demonstrate that RIalpha LLPS drives cAMP compa

62 ocalized IPMK acts as a chaperone to inhibit LLPS of TFEB to negatively control its transcriptional a

63 IPMK directly interacts with and inhibits LLPS of TFEB and also dissolves TFEB condensates.

64 th these amide groups and therefore inhibits LLPS and NNN-cooperativity.

65 ological and pathological contexts involving LLPS requires clear standards for their study.

66 cific IRF3/IRF7 DBD site/s abolish IRF3/IRF7 LLPS and IFN-I induction.

67 Although FRQ phosphorylation favors LLPS, LLPS feeds back to reduce FRQ phosphorylation by CK1 at

68 ocal concentrations to allow for a localized LLPS driven by IDRs on RNA binding proteins.

69 and from unstructured proteins with a lower LLPS propensity and further identified such sequences fr

70 tion of several of the proteins that mediate LLPS.

71 the LCD of hnRNPA1 is sufficient to mediate LLPS, the RNA recognition motifs contribute to LLPS in t

72 We suggest that LCD-mediated LLPS contributes to the assembly of stress granules and

73 a bulk instability introduced by metastable LLPS exposed to an ion-activated attractive substrate.

74 we carried out experiments in which a model LLPS system, formed from DNA "nanostar" particles, inter

75 s show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the de

76 which bis-ANS and related compounds modulate LLPS and identify key chemical features of small molecul

77 in identifying small molecules that modulate LLPS.

78 d domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins.

79 upon PLL addition, we revealed a multistage LLPS process mediated by the long-range interactions bet

80 ationship between disease-related mutations, LLPS, and tau fibrillation.

81 reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.

82 llular and synthetic biology applications of LLPS.

83 izes recent work on the molecular aspects of LLPS of various protein systems, and discusses future op

84 or rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveat

85 relationship and functional consequences of LLPS in vivo are even more elusive.

86 slope of the tie-lines and the dependence of LLPS temperature on polymer concentration provide a powe

87 for characterizing the molecular details of LLPS to modulate phase separation.

88 imental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (

89 cer cell pathology, and the dysregulation of LLPS is increasingly implicated as a previously hidden d

90 Events of LLPS were observed for all samples with both techniques.

91 er a short lag phase without any evidence of LLPS.

92 t PEG can be used to reveal the existence of LLPS for a much wider range of binary protein-water syst

93 More recently, the importance of LLPS has been realized in the compartmentalization of li

94 nings of XCI and outline how manipulation of LLPS-based mechanisms offers new avenues for novel thera

95 We use our measurements of LLPS temperature as a function of protein and PEG concen

96 ional design of small molecule modulators of LLPS with therapeutic value.

97 g release and hence the occurrence or not of LLPS upon ASD dissolution.

98 se of drug and polymer and the occurrence of LLPS and secondly, the switch between congruent and inco

99 des play the role of a modulator/promoter of LLPS in cells using computational methods.

100 like liquid droplets, many ramifications of LLPS including nucleolar dynamics and interactions with

101 RBPs have emerged as important regulators of LLPS and RNP granule dynamics, as they can directly weak

102 , the nucleation and initial growth steps of LLPS could be captured, opening the door for a deeper un

103 ts can influence the critical temperature of LLPS.

104 At a ~1:1 ratio of N to oligonucleotide, LLPS formation is maximal.

105 the deep sea, studies of pressure effects on LLPS as presented here are relevant to the possible form

106 ends lead to only a modest overall impact on LLPS.

107 We show that our LLPS measurements can be also used to estimate the prote

108 after photobleaching consistent with the PRD LLPS in vitro.

109 ed proteins disengages networks and prevents LLPS.

110 contain amino acid compositions that promote LLPS.

111 heavily into the droplet phase and promoted LLPS.

112 We found that the wild-type IDR promotes LLPS of the polySH3-polyPRM system, decreasing the phase

113 residues is a sequence feature that promotes LLPS while inhibiting aggregation.

114 describe the bacterial systems with proposed LLPS activity, and we comment on the general role LLPS p

115 structural technique to characterize protein LLPS due to the variety and specificity of information t

116 our recently developed HPS model for protein LLPS, allows us to capture the factors driving protein-p

117 ds are potent biphasic modulators of protein LLPS.

118 critical points as pure systems or, if pure LLPS is unfeasible, as binary scaffold-client mixtures.

119 Our work reveals LLPS as a principal organizer of signaling compartments

120 typical liver cancer potently blocks RIalpha LLPS and induces aberrant cAMP signaling.

121 Loss of RIalpha LLPS in normal cells increases cell proliferation and in

122 MP-induced LLPS, we demonstrate that RIalpha LLPS drives cAMP compartmentalization to tune beta cell

123 or heterotypic peptide-RNA and homotypic RNA LLPS, which results in a switch between coacervate types

124 s exert interaction-dependent effects on RNA LLPS.

125 xperiment and simulation reveal that tau-RNA LLPS is stable within a narrow equilibrium window near p

126 Robust LLPS with RNA requires two intrinsically disordered regi

127 activity, and we comment on the general role LLPS plays in bacteria and how it may regulate cellular

128 described as liquid-liquid phase separation (LLPS) accompanied by gelation within the protein-rich ph

129 SF6 displays liquid-liquid phase separation (LLPS) activity in vitro, the contributions of its differ

130 a) undergoes liquid-liquid phase separation (LLPS) and forms liquid droplets and gels in vitro, prope

131 rP undergoes liquid-liquid phase separation (LLPS) and if this process is modulated by NAs.

132 can undergo liquid-liquid phase separation (LLPS) and proposed that the inner centromere is a membra

133 mble through liquid-liquid phase separation (LLPS) and suggest that phase-separated condensates can o

134 with RNA via liquid-liquid phase separation (LLPS) and that N protein can be recruited in phase-separ

135 es formed by liquid-liquid phase separation (LLPS) are considered one of the early compartmentalizati

136 mble through liquid-liquid phase separation (LLPS) arising from interactions distributed unevenly acr

137 a, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecul

138 we identify liquid-liquid phase separation (LLPS) as a mechanism for organizing clusters of RNA poly

139 nstance, use liquid-liquid phase separation (LLPS) as the precursor phase to form various fibrillar o

140 ave observed liquid-liquid phase separation (LLPS) at -8 degrees C and revealed that, in the binary g

141 ver a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 m

142 n to undergo liquid liquid phase separation (LLPS) both in vivo and in vitro.

143 approaching liquid-liquid phase separation (LLPS) by changing protein concentration (c(p)) or temper

144 Liquid-liquid phase separation (LLPS) compartmentalizes transcriptional condensates for

145 system near Liquid-Liquid Phase Separation (LLPS) conditions by both sitting-drop vapour diffusion a

146 an important liquid-liquid phase separation (LLPS) driver for other types of AGGF1-positive nuclear c

147 formation by liquid-liquid phase separation (LLPS) facilitates the initial steps of ribosome biogenes

148 Liquid-liquid phase separation (LLPS) has been recognized as one of the key cellular org

149 ents through liquid-liquid phase separation (LLPS) has challenged long-standing notions of how protei

150 s to undergo liquid-liquid phase separation (LLPS) in cells.

151 s) can drive liquid-liquid phase separation (LLPS) in cells.

152 tail-driven liquid-liquid phase separation (LLPS) in physiologic salt and when microinjected into ce

153 ilitates its liquid-liquid phase separation (LLPS) in the nucleolus.

154 motes TDP-43 liquid-liquid phase separation (LLPS) in vitro.

155 s, undergoes liquid-liquid phase separation (LLPS) in vitro.

156 s to undergo liquid-liquid phase separation (LLPS) in vitro.

157 A1 undergoes liquid-liquid phase separation (LLPS) into protein-rich droplets mediated by a low compl

158 lications of liquid-liquid phase separation (LLPS) is increasingly of interest, its relationship with

159 Liquid-liquid phase separation (LLPS) is involved in the formation of membraneless organ

160 Liquid-liquid phase separation (LLPS) is one proposed mechanism for membraneless organel

161 Liquid-liquid phase separation (LLPS) is thought to contribute to the establishment of m

162 he idea that liquid-liquid phase separation (LLPS) may be a general mechanism by which molecules in t

163 Liquid-liquid phase separation (LLPS) mediates formation of membraneless condensates suc

164 imicking the liquid-liquid phase separation (LLPS) observed in proteins to create coacervate droplets

165 Liquid-liquid phase separation (LLPS) occurs following amorphous solid dispersion (ASD)

166 roteinaceous liquid-liquid phase separation (LLPS) occurs when a polypeptide coalesces into a dense p

167 (PEG) on the liquid-liquid phase separation (LLPS) of aqueous solutions of bovine gammaD-crystallin (

168 akening that liquid-liquid phase separation (LLPS) of key protein and nucleic acid scaffolds underpin

169 re formed by liquid-liquid phase separation (LLPS) of multivalent molecules.

170 t phase upon liquid-liquid phase separation (LLPS) of protein or protein-RNA mixtures, mediate myriad

171 Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a phenomenon that

172 ndensates is liquid-liquid phase separation (LLPS) of proteins and nucleic acids.

173 or transient liquid-liquid phase separation (LLPS) of proteins and other biomolecules.

174 Liquid-liquid phase separation (LLPS) of proteins into concentrated microdroplets (also

175 Liquid-liquid phase separation (LLPS) of proteins that leads to formation of membrane-le

176 Liquid-liquid phase separation (LLPS) of proteins underlies the formation of membrane-le

177 underlain by liquid-liquid phase separation (LLPS) of proteins, we conducted multiple-chain simulatio

178 Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in

179 Liquid-liquid phase separation (LLPS) of RNA-protein complexes plays a major role in the

180 hat leads to liquid-liquid phase separation (LLPS) of the tau protein, whose pathological aggregation

181 ding-induced liquid/liquid phase separation (LLPS) on the dynamic spatial organization of FtsZ, the m

182 s formed via liquid-liquid phase separation (LLPS) play a crucial role in the spatiotemporal organiza

183 e process of liquid-liquid phase separation (LLPS) play diverse roles inside cells, from spatiotempor

184 Cellular liquid-liquid phase separation (LLPS) plays a key role in the dynamics and function of R

185 gests that a liquid-liquid phase separation (LLPS) process may drive their formation, possibly justif

186 rocesses use liquid-liquid phase separation (LLPS) to create functional levels of organization, but t

187 y undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the gen

188 al. show how liquid-liquid phase separation (LLPS) under hyperosmotic stress conditions allows cells

189 ounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartmen

190 eciated that liquid-liquid phase separation (LLPS) underlies the formation of membraneless organelles

191 ly undergoes liquid-liquid phase separation (LLPS) upon binding DNA in vitro.

192 ns including liquid-liquid phase separation (LLPS) while responding to changes in the ambient relativ

193 n) undergoes liquid-liquid phase separation (LLPS) with viral RNA.

194 el undergoes liquid-liquid phase separation (LLPS) within nuclei in multiple cell types.

195 hat form via liquid-liquid phase separation (LLPS)(1,2).

196 ompletion of liquid-liquid phase separation (LLPS), a process by which aqueous solutions demix into 2

197 ormation via liquid-liquid phase separation (LLPS), a process underlying the formation of membraneles

198 d to form by liquid-liquid phase separation (LLPS), a thermodynamic process that partitions molecules

199 LC) mediates liquid-liquid phase separation (LLPS), but the interactions between the repetitive SYGQ-

200 can undergo liquid-liquid phase separation (LLPS), forming dense droplets that are increasingly unde

201 can undergo liquid-liquid phase separation (LLPS), forming highly dynamic liquid droplets.

202 ly undergoes liquid-liquid phase separation (LLPS), here we explored the relationship between disease

203 ssembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartment

204 e process of liquid-liquid phase separation (LLPS), play key roles in RNA metabolism and cellular org

205 ts formed by liquid-liquid phase separation (LLPS), represent an important mechanism for physiologica

206 ly formed by liquid-liquid phase separation (LLPS), they have a differential sensitivity to hypotonic

207 form through liquid-liquid phase separation (LLPS), whereby weak promiscuous interactions among RBPs

208 WI-catalyzed liquid-liquid phase separation (LLPS), which initiates hydrogelation and aggregation.

209 at undergoes liquid-liquid phase separation (LLPS).

210 ocess termed liquid-liquid phase separation (LLPS).

211 s that drive liquid-liquid phase separation (LLPS).

212 y to undergo liquid-liquid phase separation (LLPS).

213 y to undergo liquid-liquid phase separation (LLPS).

214 m to undergo liquid-liquid phase separation (LLPS).

215 e formed via liquid-liquid phase separation (LLPS).

216 mechanism of liquid-liquid phase separation (LLPS).

217 to form via liquid-liquid phase separation (LLPS).

218 y to undergo liquid-liquid phase separation (LLPS).

219 ates through liquid-liquid phase separation (LLPS).

220 hich undergo liquid-liquid phase separation (LLPS).

221 e formed via liquid-liquid phase separation (LLPS).

222 can undergo liquid-liquid phase separation (LLPS); however, observations of this phase transition in

223 that alter liquid-liquid phase separations (LLPS) driven by intrinsically disordered protein regions

224 on machinery, has been studied using several LLPS systems.

225 SHP2 LLPS is mediated by the conserved well-folded PTP domain

226 rforming the molecular dynamics simulations, LLPS can be observed at low temperatures even without ch

227 ical studies have suggested that spontaneous LLPS of the RNA-binding protein PGL-3 with RNA drives th

228 c interactions all contribute to stabilizing LLPS of FUS LC.

229 patially by gel-like polymers that stimulate LLPS locally in the cytoplasm.

230 view discusses practical aspects of studying LLPS by NMR, summarizes recent work on the molecular asp

231 acromolecular regulators promote or suppress LLPS.

232 oderate partition coefficient and suppressed LLPS by substituting weaker attraction with SH3(5) for t

233 PY-NLS, can still bind KapB2 and suppresses LLPS.

234 hobic, and n-driven interactions can sustain LLPS for suitable polypeptide sequences.

235 could inform antiviral strategies targeting LLPS.

236 ons, phosphorylation is not required for tau LLPS.

237 anslational modifications could modulate tau LLPS in the context of specific physiological functions

238 We observed no tau LLPS-promoting effect for any other divalent transition

239 into the thermodynamic driving forces of tau LLPS.

240 Here, we demonstrate that tau LLPS is largely driven by intermolecular electrostatic i

241 While it has been established that LLPS can be described as a spinodal decomposition leadin

242 number of recent observations indicate that LLPS may also play a role in disease.

243 We show that LLPS-HS promotes tau protein dehydration, undergoes matu

244 These combined results strongly suggest that LLPS may play a major role in pathological TDP-43 aggreg

245 These results not only suggest that LLPS serves as a gain-of-function mechanism involved in

246 rosine-to-phenylalanine mutants suggest that LLPS-driving phenylalanine interactions are significantl

247 The LLPS concept is also likely useful in designing new ther

248 reduces the condensate formation during the LLPS process.

249 oth saline and crowded settings enhanced the LLPS propensity.

250 Our results extend and enrich the LLPS framework by showing the impact of the surrounding

251 For the LLPS particles, the fRHext at each RH was between the fR

252 inc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mech

253 n X-ray microscopy (STXM) to investigate the LLPS of micrometer-sized particles undergoing a full hyd

254 e of this minor species is the result of the LLPS occurring concomitantly under crystallization condi

255 Finally, we show that the increase of the LLPS temperature with PEG concentration is due to attrac

256 lar scenario underlying the emergence of the LLPS-to-fibrils pathway in the ACC(1-13)K(n)-ATP system

257 filaments is determined by the nature of the LLPS.

258 e effects of temperature and pressure on the LLPS of the eye-lens protein gamma-crystallin using UV/v

259 both the effect of PEG concentration on the LLPS temperature and proteinPEG partitioning between the

260 The sequence features which reflect the LLPS behavior are also available for other human protein

261 We suggest that the LLPS model provides the starting point for a unifying qu

262 We furthermore show that the LLPS process is directly and sensitively tuned by salt c

263 Quite unexpectedly, the LLPS of gamma-crystallin is much more sensitive to press

264 omolecular condensates that assemble through LLPS.

265 PS, the RNA recognition motifs contribute to LLPS in the presence of RNA, giving rise to several mech

266 dues also participate in contacts leading to LLPS of FUS LC.

267 and C-terminal mixed-charge domain (MCD), to LLPS activity and to HIV-1 infection remain unclear.

268 has been paid to the contribution of RNA to LLPS.

269 agram, we show that tau can be driven toward LLPS under live cell coculturing conditions with rationa

270 showed marked signatures of a ligand-tunable LLPS process.

271 fibrillation and that its aggregation under LLPS conditions involves several distinct events, culmin

272 lts from unique properties of proteins under LLPS conditions, where total concentration of all tau va

273 the concentration at which the drugs undergo LLPS in the presence of other miscible drugs, thereby re

274 peat domain and histidines, does not undergo LLPS and forms nondynamic protein assemblies indicative

275 h shows reduced Cu-binding, does not undergo LLPS.

276 cleotide repeat expansions similarly undergo LLPS and induce phase separation of a large set of prote

277 ationic amino acids in proteins that undergo LLPS, with arginine-rich proteins observed to undergo LL

278 90-231) and modulated its ability to undergo LLPS and fibrillate.

279 xplore how the ability of the CPC to undergo LLPS may contribute to the organization and function of

280 h arginine-rich proteins observed to undergo LLPS more readily than lysine-rich proteins, a feature c

281 Proteins that are able to undergo LLPS often contain intrinsically disordered regions and

282 TDP-43 is present in several MLOs, undergoes LLPS, and has been linked to the pathogenesis of amyotro

283 We show here that PrP undergoes LLPS, and that the PrP interaction with NAs modulates ph

284 TFEB undergoes LLPS in vitro.

285 he intermolecular interactions that underlie LLPS and aggregation and the underlying mechanisms facil

286 he thermodynamic free energies that underlie LLPS.

287 actions involving all residue types underlie LLPS of human FUS LC.

288 nly ASDs showing congruent release underwent LLPS, with the formation of amorphous drug-rich aggregat

289 d glycine repeats of NUP98 with an unrelated LLPS-forming IDR of the FUS protein(3,4), had similar en

290 ct but mutually complementary roles that use LLPS in a cellular context to implement emergent functio

291 Despite clear biological utility, LLPS can also have deleterious outcomes.

292 onegavirales have broadly evolved to utilize LLPS as a common strategy to assemble cytoplasmic replic

293 We find that the evidence for in vivo LLPS is often phenomenological and inadequate to discrim

294 of swc chains are found to be coexisted when LLPS occurs.

295 myloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrog

296 ated RNA-binding capacity determines whether LLPS occurs upon RNA influx.

297 co-existence is key to understanding whether LLPS is an equilibrium or intermediate state.

298 a previously unrecognized mechanism by which LLPS can regulate the rate of fibrillation in mixtures c

299 rectly leads to canonical tau fibrils, while LLPS-ED is reversible, remains hydrated and does not pro

300 By analogy with LLPS in binary solutions, cellular LLPS was hypothesized