llps  (MedChemExpress)

Journal: International Journal of Molecular Sciences

Article Title: Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell

doi: 10.3390/ijms27083478

Figure Lengend Snippet: Evolutionary trajectory of TERT: from rigid catalyst to liquid-state driver. ( A ) Structural stability in invertebrates: The TERT ortholog from T. castaneum (PDB ID: 7QKM) represents the ancestral, predominantly ordered state. FuzDrop profiling reveals a low droplet-promoting probability (p LLPS : 0.11), where the protein acts as a rigid enzymatic unit. ( B ) LLPS expansion in mammals: Human TERT exhibits a significant rise in intrinsic disorder (31.43%) and p LLPS (0.62). Domain mapping shows that liquidity peaks coincide with RNA-interacting motifs (GQ, CP, and QFP) and the Nuclear Localization Signal (NLS), suggesting that in higher eukaryotes, TERT functions as an active organizer of telomeric condensates. ( C ) The “L-paradox” across taxa: Large-scale analysis reveals that while intrinsic disorder remains relatively conserved (28–38% across vertebrates), the propensity for phase separation (pLLPS) exhibits sharp, lineage-specific oscillations. This “L-paradox” (liquidity paradox) indicates that phase behavior acts as an evolutionary “switch” or rheostat, with outliers like the lamprey and domestic cat (marked with red stars) showing extreme spikes in liquidity. This variability likely reflects lineage-specific adaptations in genomic maintenance, metabolic rate, and cellular longevity.

Article Snippet: Taxon-dependent clustering: Our results show clear phylogenetic clustering of p LLPS values ( C).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell

doi: 10.3390/ijms27083478

Figure Lengend Snippet: Biophysical landscapes of Arc orthologs and Gag-related proteins. (Top) 3D structures (PDB), residue-based droplet-promoting probabilities (p DP ), predicted regions of disorder, aggregation, and context-dependent binding (FuzDrop/FuzPred), and UniProt domains/features aligned with the p DP graph of ( A ) D. melanogaster (dArc2) and ( B ) H. sapiens (Arc), illustrating the evolutionary transition from rigid invertebrate architecture to high-disorder and LLPS propensity mammalian condensates. (Bottom) ( C ) Comparative analysis of p LLPS propensity, protein disorder, and amyloidogenic potential across 30+ species. Left Y-axis: p LLPS and disorder scores (0.0–1.0). Right Y-axis: Number of amyloidogenic segments (PASTA 2.0). Yellow/Pink bars: Evolutionary benchmarks (HIV-1 Gag, PERV Gag, and PEG10) revealing the high ancestral propensity for phase separation and aggregation. Light-blue bars: Drosophila convergent homologs (dArc1, dArc2); dark-blue bars: vertebrate orthologs, highlighting the significant “mammalian shift” in p LLPS . Red dots: Amyloidogenic potential, showing discrete “quantal” plateaus (7–8 for Sauropsids vs. 38 for Eutherians). Stars: Red and blue stars denote significant outliers in amyloidogenic potential (notably the Indian elephant) and p LLPS propensity, respectively. Note: The proposed evolutionary trajectories and “quantum leaps” of these biophysical parameters are discussed in detail within the main text .

Article Snippet: Taxon-dependent clustering: Our results show clear phylogenetic clustering of p LLPS values ( C).

Techniques: Residue, Binding Assay

Journal: bioRxiv

Article Title: Wetting-mediated extracellular phase separation drives long-range cell adhesion

doi: 10.64898/2026.01.23.700778

Figure Lengend Snippet: a Bright-field and confocal images of Jurkat cells incubated with a high concentration (10 µ M) of GFP-tagged Galectin-3 (GAL3-GFP), showing extensive cell aggregation and surface coating. Scale bar, 10 µ m. b High-resolution 3D reconstruction of a cell cluster from a , revealing GAL3-GFP condensates (green) at cell–cell junctions, acting as a “liquid glue”. Scale bar, 5 µ m. c Aggregation and surface wetting observed at an intermediate GAL3-GFP concentration (1 µ M). Scale bar, 10 µ m. d Aggregation and surface wetting observed at a low GAL3-GFP concentration (100 nM). Scale bar, 10 µ m. e Validation of LLPS-dependent aggregation. Robust clustering is observed at 10 µ M and 1 µ M GAL3, but aggregation is abrogated in PBS buffer and with an LLPS-deficient GAL3 mutant. f Time-lapse microscopy showing the liquid-like behaviour of condensates: two smaller droplets coalesce into a larger spherical droplet over ~46 s. g Quantitative FRAP curves of GAL3-GFP on Jurkat cell surfaces at different concentrations. h Aggregation kinetics, tracking the number of clusters over time and showing that higher GAL3 concentrations lead to faster and more extensive aggregation.

Article Snippet: Galectin-3 and CCL5 exemplify how extracellular LLPS can function in a specific, concentration-dependent manner to promote multicellular organisation.

Techniques: Incubation, Concentration Assay, Biomarker Discovery, Mutagenesis, Time-lapse Microscopy

Journal: bioRxiv

Article Title: Wetting-mediated extracellular phase separation drives long-range cell adhesion

doi: 10.64898/2026.01.23.700778

Figure Lengend Snippet: a Conceptual illustration of biomolecular condensate-mediated cell–cell contact and signaling enhancement, using a CD27/CD70 Jurkat–Raji reporter system to demonstrate that LLPS-driven bridges enhance intercellular signaling efficiency. b Comparison of experimental and simulated cell–cell interactions mediated by a phase-separating medium. c Confocal images of the reporter system mediated by DEX (green, DEX–FITC). Jurkat cells (red, Cytotell Orange) and Raji cells (blue, Cytotell Blue) interact in different morphological regimes. Scale bar, 10 µ m. d Reporter signal kinetics (RLU vs. time) in the bulk binodal regime. Various DEX volume fractions ( ϕ DEX ) all show significant signal enhancement compared to blank and positive controls. e Reporter signal kinetics in the bulk one-phase regime. Nanomolar DEX concentrations (200 nM, 400 nM) induce rapid activation, with initial kinetics even faster than those in the binodal regime. f Confocal microscopy images of Jurkat (red) and Raji (blue) cells in the bulk one-phase regime mediated by FUS protein. Scale bars, 10 µ m. g Quantification of downstream signaling (CD27/CD70 Jurkat–Raji reporter assay, RLU) in a co-culture system with 2500 nM FUS protein over time, compared to positive and blank controls and to higher DEX concentration (100 nM).

Article Snippet: Galectin-3 and CCL5 exemplify how extracellular LLPS can function in a specific, concentration-dependent manner to promote multicellular organisation.

Techniques: Comparison, Activation Assay, Confocal Microscopy, Reporter Assay, Co-Culture Assay, Concentration Assay