Nanoscale Liquid Research Articles

Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines.

Cancer is characterized by the development of abnormal cells that divide in an uncontrolled way and may spread into other tissues where they may infiltrate and destroy normal body tissue. Several previous reports have described biochemical anti-tumorigenic properties of crude snake venom or its components, including their capability of inhibiting cell proliferation and promoting cell death. However, to the best of our knowledge, there is no work describing cancer cell proteomic changes following treatment with snake venoms. In this work we describe the quantitative changes in proteomics of MCF7 and MDA-MB-231 breast tumor cell lines following treatment with Bothrops jararaca snake venom, as well as the functional implications of the proteomic changes. Cell lines were treated with sub-toxic doses at either 0.63 μg/mL (low) or 2.5 μg/mL (high) of B. jararaca venom for 24 h, conditions that cause no cell death per se. Proteomics analysis was conducted on a nano-scale liquid chromatography coupled on-line with mass spectrometry (nLC-MS/MS). More than 1000 proteins were identified and evaluated from each cell line treated with either the low or high dose of the snake venom. Protein profiling upon venom treatment showed differential expression of several proteins related to cancer cell metabolism, immune response, and inflammation. Among the identified proteins we highlight histone H3, SNX3, HEL-S-156an, MTCH2, RPS, MCC2, IGF2BP1, and GSTM3. These data suggest that sub-toxic doses of B. jararaca venom have potential to modulate cancer-development related protein targets in cancer cells. This work illustrates a novel biochemical strategy to identify therapeutic targets against cancer cell growth and survival.

Relaxation of Thermal Capillary Waves for Nanoscale Liquid Films on Anisotropic-Slip Substrates.

The relaxation dynamics of thermal capillary waves for nanoscale liquid films on anisotropic-slip substrates are investigated using both molecular dynamics (MD) simulations and a Langevin model. The anisotropy of slip on substrates is achieved using a specific lattice plane of a face-centered cubic lattice. This surface's anisotropy breaks the simple scalar proportionality between slip velocity and wall shear stress and requires the introduction of a slip-coefficient tensor. The Langevin equation can describe both the growth of capillary wave spectra and the relaxation of capillary wave correlations, with the former providing a time scale for the surface to reach thermal equilibrium. Temporal correlations of interfacial Fourier modes, measured at thermal equilibrium in MD, demonstrate that (i) larger slip lengths lead to a faster decay in wave correlations and (ii) unlike isotropic-slip substrates, the time correlations of waves on anisotropic-slip substrates are wave-direction-dependent. These findings emerge naturally from the proposed Langevin equation, which becomes wave-direction-dependent, agrees well with MD results, and allows us to produce experimentally verifiable predictions.

Abstract 1008: Comparative proteomics and transcriptomics analysis of the impact of androgen stimulation and darolutamide inhibition in a prostate cancer model

Abstract Androgen receptor (AR) signaling is the major driver in prostate cancer. Darolutamide is a high-affinity AR inhibitor recently approved for non-metastatic castration-resistant prostate cancer. The impact of the AR on gene transcription has been extensively examined but the downstream effects on protein levels are still poorly understood. Here we generated for the first time comprehensive quantitative proteomic and transcriptomic data from the androgen-sensitive, prostate cancer cell line VCaP treated with the androgen R1881 and darolutamide. For the proteomic analysis, a comprehensive and quantitative label-free protein expression profiling was performed using nanoscale liquid chromatography coupled to tandem mass spectrometry. For the transcriptomic analysis, sequencing was performed via single-end, 50 base-pair reads with an average depth of 21 million reads per sample. FASTQ reads were mapped with STAR aligner to the human genome GRCh38 and quantified with RSEM. Further analysis was performed in R statistical software. We investigated the expression levels of 12900 protein-coding genes and 8721 translated proteins. Androgen treatment resulted in increased expression of known androgen response genes, as well as of genes from the mTORC1 pathway, cell cycle and other pathways previously shown to be affected by androgens. This was paralleled by upregulation of the corresponding protein levels in the majority of cases. Importantly, a detailed comparative analysis of transcriptomic and proteomic data revealed a few notable differences in regulation. In androgen-treated prostate cancer cells, there was a strong increase of FOLH1, AMACR and FKBP5 transcript levels (10 to 40-fold) but only a moderate increase of the corresponding protein levels (2 to 6-fold). Additional darolutamide treatment led to strong down-regulation of androgen-induced gene expression and of the corresponding protein levels. Here also there were a few instances where protein and transcript levels were differentially regulated. The discrepancy in transcript and protein levels seen after androgen and anti-androgen treatment suggests differential post-transcriptional regulation of protein abundance to occur in some instances. In conclusion, we found that darolutamide strongly reversed androgen-induced activation of gene expression programs related to cell proliferation and survival, both at the transcript and protein levels. We furthermore identified for the first time androgen-activated genes whose function is additionally regulated at the post-transcription level. Citation Format: Ekaterina Nevedomskaya, Simon J. Baumgart, Tatsuo Sugawara, Ralf Lesche, Dominik Mumberg, Bernard Haendler. Comparative proteomics and transcriptomics analysis of the impact of androgen stimulation and darolutamide inhibition in a prostate cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1008.

Antioxidant and anti-inflammatory properties of novel peptides from Moringa oleifera Lam. leaves

Moringa oleifera is a tree used as a medicinal herb by several populations. Due to their curative and preventive properties, all parts have been studied, especially the leaves. They have been found to act as antithrombotic, antihypertensive, anticancer, immunomodulating, and antioxidant agents. This study was aimed to characterize and evaluate the antioxidant and anti-inflammation activities of Moringa oleifera leaves protein hydrolysate obtained by in vitro gastrointestinal digestion. The antioxidant activity of these peptides was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and Oxygen Radical Absorbance Capacity (ORAC) assays. RAW 264.7 macrophages were stimulated with lipopolysaccharides, and the effect of the peptides over nitric oxide production was measured to assess the anti-inflammatory effect. Furthermore, peptides were identified by nanoscale liquid chromatography coupled to tandem mass spectrometry. Moringa oleifera leaves peptides (1.33 mg/ml) inhibited DPPH and ABTS radicals by 45.70 and 93.09%, respectively, and had an ORAC activity of 3.27 mM Trolox equivalent/g. They were not cytotoxic to lipopolysaccharides-induced RAW 264.7 macrophages and, at a concentration of 100 μg/ml, inhibited the nitric oxide production by 30.51%. The sequences of 14 novel peptides were identified. Our findings suggest that Moringa oleifera leaves peptides released by in vitro gastrointestinal digestion might be a potential resource for natural antioxidant and anti-inflammatory components. However, further in vivo experiments are needed.

TMT-based quantitative proteomics analysis reveals the key proteins related with the differentiation process of goat intramuscular adipocytes

BackgroundIntramuscular adipocytes differentiation is a complex process, which is regulated by various transcription factor, protein factor regulators and signal transduction pathways. However, the proteins and signal pathways that regulates goat intramuscular adipocytes differentiation remains unclear.ResultIn this study, based on nanoscale liquid chromatography mass spectrometry analysis (LC-MS/MS), the tandem mass tag (TMT) labeling analysis was used to investigate the differentially abundant proteins (DAPs) related with the differentiation process of goat intramuscular adipocytes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment and protein-protein interaction network analyses were performed for the characterization of the identified DAPs. The candidate proteins were verified by parallel reaction monitoring analysis. As a result, a total of 123 proteins, 70 upregulation proteins and 53 downregulation proteins, were identified as DAPs which may be related with the differentiation process of goat intramuscular adipocytes. Furthermore, the cholesterol metabolism pathway, glucagon signaling pathway and glycolysis / gluconeogenesis pathway were noticed that may be the important signal pathways for goat Intramuscular adipocytes differentiation.ConclusionsBy proteomic comparison between goat intramuscular preadipocytes (P_IMA) and intramuscular adipocytes (IMA), we identified a series protein that might play important role in the goat intramuscular fat differentiation, such as SRSF10, CSRP3, APOH, PPP3R1, CRTC2, FOS, SERPINE1 and AIF1L, could serve as candidates for further elucidate the molecular mechanism of IMF differentiation in goats.

Acylated peptide enrichment utilizing lysine deacylases for lysine acylomics

Reversible acylation of lysine ε-amino groups, e.g., acetylation, succinylation, maronylation, and myristoylation, is involved in basic physiological processes such as metabolism, cell signaling and aging. In this study, we developed a novel enrichment method for acylated peptides without the use of antibodies, in which endogenously acylated peptides are deacylated by recombinant lysine deacylases based on the enzyme-substrate relationship and enriched by N-hydroxysuccinimidyl chemistry for identification of the acylated sites by nanoscale liquid chromatography-tandem mass spectrometric analysis. To demonstrate the validity of this acylomics platform, we used it to identify acylated sites on chemically acylated model protein samples. We also applied it to the nuclei of HeLa cells to identify endogenous acylated sites.

Dynamics of nanoscale thin liquid films during coalescence and chemical reaction of droplets

The understanding of flow characteristics and interface structure evolution during the chemical reaction of droplets are important for many industrial processes. In this paper, qualitative observation and quantitative measurement are implemented at the region near the contact line of acetic acid and ammonium hydroxide droplets to study the flow field and interface evolution during the neutralization reaction of these testing fluids by an observation technique based on evanescent wave illumination. A three-dimensional sub-region method for characterizing the interface structure of the thin liquid film during droplet reaction is developed. The interface structures and velocity fields of the thin liquid films obtained by this method reveal that at the moment of reaction the mesoscopic interface structure deforms severely and the convex interfaces appear at the central regions due to the impact of the initial kinetic energy and the chemical reaction of droplets. Meanwhile, the reaction rate is found to decrease exponentially with the increase of height in the thin liquid film. The work provides valuable information for further understanding the mechanisms of formation and transport of the mesoscale interface structure during chemical reactions.

Atomistic Insight into the Effects of Depositional Nanoparticle on Nanoscale Liquid Film Evaporation.

Nanoscale liquid film evaporation plays an essential role in many engineering applications. This study carries out molecular dynamics simulations on the effects of the depositional nanoparticle's wettability and volume in base fluid on the evaporation process to understand how the depositional nanoparticle affects the evaporation heat transfer. Increasing the nanoparticle's wettability can enhance the evaporation heat transfer process, and the enhancement effect of the hydrophobic surface is more remarkable than that of the hydrophilic surface. This because the increasing wettability causes more significant solid-liquid interaction. However, the potential energy of argon atoms at the liquid-vapor interface is almost unaffected by wettability. Moreover, when the depositional nanoparticle locates below the free liquid film, increasing the nanoparticle volume has a better heat transfer performance. As the volume increases, the heat transfer through the nanoparticle becomes more obvious, which effectively enhances the heat transfer at the solid-liquid interface and the liquid-vapor interface. The latent heat of phase change at the liquid-vapor interface is almost unchanged so that the evaporation can be enhanced. This research provides an understanding of the effects of depositional nanoparticles on nanoscale evaporation, which can impact several engineering applications, including devices' cooling and fluid transport.

Thermal capillary wave growth and surface roughening of nanoscale liquid films

The well-known thermal capillary wave theory, which describes the capillary spectrum of the free surface of a liquid film, does not reveal the transient dynamics of surface waves, e.g. the process through which a smooth surface becomes rough. Here, a Langevin model is proposed that can capture this dynamics, goes beyond the long-wave paradigm which can be inaccurate at the nanoscale, and is validated using molecular dynamics simulations for nanoscale films on both planar and cylindrical substrates. We show that a scaling relation exists for surface roughening of a planar film and the scaling exponents belong to a specific universality class. The capillary spectra of planar films are found to advance towards a static spectrum, with the roughness of the surface $W$ increasing as a power law of time $W\sim t^{1/8}$ before saturation. However, the spectra of an annular film (with outer radius $h_0$ ) are unbounded for dimensionless wavenumber $qh_0<1$ due to the Rayleigh–Plateau instability.

From ELISA to Immunosorbent Tandem Mass Spectrometry Proteoform Analysis: The Example of CXCL8/Interleukin-8.

With ELISAs one detects the ensemble of immunoreactive molecules in biological samples. For biomolecules undergoing proteolysis for activation, potentiation or inhibition, other techniques are necessary to study biology. Here we develop methodology that combines immunosorbent sample preparation and nano-scale liquid chromatography—tandem mass spectrometry (nano-LC-MS/MS) for proteoform analysis (ISTAMPA) and apply this to the aglycosyl chemokine CXCL8. CXCL8, the most powerful human chemokine with neutrophil chemotactic and –activating properties, occurs in different NH2-terminal proteoforms due to its susceptibility to site-specific proteolytic modification. Specific proteoforms display up to 30-fold enhanced activity. The immunosorbent ion trap top-down mass spectrometry-based approach for proteoform analysis allows for simultaneous detection and quantification of full-length CXCL8(1-77), elongated CXCL8(-2-77) and all naturally occurring truncated CXCL8 forms in biological samples. For the first time we demonstrate site-specific proteolytic activation of CXCL8 in synovial fluids from patients with chronic joint inflammation and address the importance of sample collection and processing.

Quantitative Proteomics Analysis for the Identification of Differential Protein Expression in Calf Muscles between Young and Old SD Rats Using Mass Spectrometry.

Aging is associated with loss of muscle mass and strength that leads to a condition termed sarcopenia. Impaired conditions, morbidity, and malnutrition are the factors of devaluation of muscle fibers in aged animals. Satellite cells play an important role in maintaining muscle homeostasis during tissue regeneration and repair. Proteomic profiling on the skeletal muscle tissues of different age group rats helps to determine the differentially expressed (DE) proteins, which may eventually lead to the development of biomarkers in treating the conditions of sarcopenia. In this study, nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis was implemented in the calf tissues of young and old groups of rats. The mass spectrometry (MS) analysis revealed the presence of 335 differentially expressed proteins between the two different age conditions, among which those based on log-fold change 25 proteins were upregulated and 77 were downregulated. The protein–protein interaction network analysis revealed 18 upregulated proteins with three distinct interconnected networks and 57 downregulated proteins with two networks. Further, gene ontology (GO) enrichment analysis showed the biological process, cellular component, and molecular function of the differential proteins. Pathway enrichment analysis of the DE proteins identified nine significantly enriched pathways with a list of eight significant genes (Cryab, Hspb2, Acat1, Ak1, Adssl1, Anxa5, Gys1, Ogdh, Gc, and Adssl1). Quantification of significant genes by quantitative real-time polymerase chain reaction (qRT-PCR) confirmed the downregulation at the mRNA level. Western blot analysis of their protein expression showed concordant results on two candidate proteins (Ogdh and annexin 5) confirming their differential regulation between the two age groups of rats. Thus, these proteomic approaches on young and aged rats provide insights into the development of protein targets in the treatment of sarcopenia (muscle loss).

Marker peptide screening and species-specific authentication of Pheretima using proteomics.

Pheretima is a common and valuable animal-derived medication used in traditional Chinese medicine. There are four species of Pheretima specified in the Chinese Pharmacopoeia (2015 edition), i.e. Pheretima aspergillum, P. vulgaris, P. guillelmi, and P. pectinifera. A recent report revealed ~ 55% of Pheretima in the commercial marketplace may be adulterated by other species, contrary to the Pharmacopoeia standard. The safety, efficacy, and authenticity of Pheretima is an important issue. Currently, the availability of specific quality-markers for the various species and effective identification methods are still limited. In this study, label-free quantification proteomics of species from Pheretima and Amynthas was carried out using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS), and marker peptides were identified based on their ion intensities using multivariate data analysis (principal component analysis and supervised partial least-squares discriminant analysis). A total of 48,476 peptides with high confidence corresponding to 13,397 proteins were identified from all samples. The marker peptides were validated by comparison with synthetic peptide reference standards using LC-MS/MS operating in a multiple-reaction monitoring mode. A multiple-peptide identification strategy was proposed for the authentication of Pheretima and subsequently applied to samples obtained from retail outlets in various regions of China. The results showed that eight out of the 15 samples tested were deemed authentic Pheretima.

Time of Detection of Prions in the Brain by Nanoscale Liquid Chromatography Coupled to Tandem Mass Spectrometry Is Comparable to Animal Bioassay.

Prions cause transmissible and inevitably fatal neurological diseases in agriculturally important animals, including bovine spongiform encephalopathy in domestic cattle, scrapie in sheep and goats, and chronic wasting disease in cervids. Because animals are largely asymptomatic throughout the course of the disease, early detection of prion disease is important. Hamsters were peripherally (ip) inoculated with hamster-adapted (Sc237) prions. By week 13 of a 14-week disease course, clinical signs appeared. A multiple-reaction-monitoring-based method was used to quantitate the amount of proteinase-K-digested prions (PrP 27-30) and the extent of methionine 213 oxidation present in the brains of infected hamsters. Detectable amounts of PrP 27-30 were present in all animals after 4 weeks. The extent of methionine 213 oxidation decreased over time. When we compared our quantitation results to those from other researchers using bioassay, we observed that consistent detection of PrP 27-30 by mass spectrometry occurs at a time when prions are reliably detected by bioassay.

Functionally selective activation of the dopamine receptor D2 is mirrored by the protein expression profiles

The development of functionally selective or biased ligands is a promising approach towards drugs with less side effects. Biased ligands for G protein-coupled receptors can selectively induce G protein activation or β-arrestin recruitment. The consequences of this selective action on cellular functions, however, are not fully understood. Here, we investigated the impact of five biased and balanced dopamine D2 receptor agonists and antagonists on the global protein expression in HEK293T cells by untargeted nanoscale liquid chromatography–tandem mass spectrometry. The proteome analysis detected 5290 protein groups. Hierarchical clustering and principal component analysis based on the expression levels of 1462 differential proteins led to a separation of antagonists and balanced agonist from the control treatment, while the biased ligands demonstrated larger similarities to the control. Functional analysis of affected proteins revealed that the antagonists haloperidol and sulpiride regulated exocytosis and peroxisome function. The balanced agonist quinpirole, but not the functionally selective agonists induced a downregulation of proteins involved in synaptic signaling. The β-arrestin-preferring agonist BM138, however, regulated several proteins related to neuron function and the dopamine receptor-mediated signaling pathway itself. The G protein-selective partial agonist MS308 influenced rather broad functional terms such as DNA processing and mitochondrial translation.

Periostin is Oncogenic and Promotes EMT in Gliomas via Inhibition of RIN1-Mediated Endocytosis of EGFR

Background: About 1/3 of all brain tumors are gliomas. Previous glioma studies have reported increased expression of Periostin (POSTN) in these cancerous tissues, but its role and mechanism in gliomas development remain unknown. Methods: Nanoscale liquid chromatography coupled to tandem mass spectrometry (Nano LC-MS/MS) and RNA sequencing were used to identify differential protein and mRNA expression in glioma samples from the clinic. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of POSTN in tissues and cells. The effects of POSTN on glioma cell migration and invasion were examined using wound-healing, transwell, and three-dimensional spheroid assays in vitro, and a xenograft nude-mouse model in vivo. POSTN’s effect on the stability, endocytosis, and degradation of EGFR was examined by immunoblotting and immunofluorescence. Truncated mutation analysis was performed to interrogate any direct interactions between POSTN and EGFR. Immunohistochemical staining was carried out to confirm the clinical significance of POSTN. Findings: In this study, POSTN was upregulated in gliomas and was associated with poor prognosis. POSTN depletion inhibited glioma epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. Furthermore, POSTN downregulation dampened EGFR signaling via promotion of EGFR endocytosis and degradation. In addition, POSTN was found to bind to EGFR and RIN1, inhibiting EGFR endocytosis and degradation, thus promoting the activation of the PI3K-AKT signaling pathway. Interpretation: These findings indicate the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation. Targeting POSTN/EGFR/RIN1 interactions may prove beneficial the treatment of gliomas. Funding Information: This work was supported by grants from National Natural Science Foundation of China (81772682), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: Our study protocol was approved by the Research Ethics Committee of Nanjing Medical University (Nanjing, Jiangsu, China).

Effects of the Interaction between Neighboring Droplets on the Stability of Nanoscale Liquid Bridges

Effects of the Interaction between Neighboring Droplets on the Stability of Nanoscale Liquid Bridges

Effect of porcine corneal stromal extract on keratocytes from SMILE-derived lenticules.

Propagating large amounts of human corneal stromal cells (hCSCs) in vitro while maintaining the physiological quality of their phenotypes is necessary for their application in cell therapy. Here, a novel medium to propagate hCSCs obtained from small incision lenticule extraction (SMILE)‐derived lenticules was investigated and the feasibility of intrastromal injection of these hCSCs was assessed. Primary hCSCs were cultured in porcine corneal stroma extract (pCSE) with RIFA medium including ROCK inhibitor Y27632, insulin‐transferrin‐selenium, fibroblast growth factor 2, L‐ascorbate 2‐phosphate and 0.5% FBS (RIFA medium + pCSE). Protein profiling of the pCSE was identified using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC‐MS/MS). After subculturing in RIFA medium + pCSE or 10% FBS normal medium (NM), hCSCs at P4 were transplanted into mouse corneal stroma. Compared with NM, ALDH3A1, keratocan and lumican were significantly more expressed in the RIFA medium + pCSE. ALDH3A1 was also more expressed in the RIFA medium + pCSE than in the RIFA medium. Fibronectin and α‐SMA were less expressed in the RIFA medium + pCSE than in the NM. Using Metascape analysis, the pCSE with its anti‐fibrosis, pro‐proliferation and anti‐apoptosis activities, was beneficial for hCSC cultivation. The intrastromally implanted hCSCs in the RIFA medium + pCSE had positive CD34 expression but negative CD45 expression 35 days after injection. We provide a valuable new medium that is advantageous for the proliferation of hCSCs with the properties of physiological keratocytes. Intrastromal injection of hCSCs in RIFA medium + pCSE has the potential for clinical cell therapy.

The Simulation of Liquid Flow in the Pore Network Model of Nanoporous Media

Abstract The fluid–solid interaction force shows significant influence on liquid flow at nanoscale. Vast experimental observations in recent literatures have shown that Darcy's law cannot be applied to nanoporous media. In this study, the slip length and effective viscosity are adapted to characterize the nanoscale effect. First, the nanoscale effect is investigated in nanotubes through computational fluid dynamic (CFD) modeling analysis. Slip boundary condition has been studied as an important discrepancy between macroscopic flow and nanoscale liquid flow. The effect of viscosity change becomes more notable with the slip length increasing. Then, the flow equation for pore network modeling is developed to capture nanoscale effect. The results show that the apparent permeability of nanoscale systems is significantly underestimated when slip effect is neglected. The size of the pore throat determines whether the slip effect needs to be considered, and critical diameter of neglecting the slip effect for circular throat is 79.17 Ls. It is necessary to take the variation of effective viscosity into account under slip boundary condition. With the pore throat size decreasing, the nanoscale effect increases. The nanoscale effect is more sensitive to pore throat size under hydrophobic conditions than hydrophilic conditions.

Micellar TIA1 with folded RNA binding domains as a model for reversible stress granule formation

TIA1, a protein critical for eukaryotic stress response and stress granule formation, is structurally characterized in full-length form. TIA1 contains three RNA recognition motifs (RRMs) and a C-terminal low-complexity domain, sometimes referred to as a "prion-related domain" or associated with amyloid formation. Under mild conditions, full-length (fl) mouse TIA1 spontaneously oligomerizes to form a metastable colloid-like suspension. RRM2 and RRM3, known to be critical for function, are folded similarly in excised domains and this oligomeric form of apo fl TIA1, based on NMR chemical shifts. By contrast, the termini were not detected by NMR and are unlikely to be amyloid-like. We were able to assign the NMR shifts with the aid of previously assigned solution-state shifts for the RRM2,3 isolated domains and homology modeling. We present a micellar model of fl TIA1 wherein RRM2 and RRM3 are colocalized, ordered, hydrated, and available for nucleotide binding. At the same time, the termini are disordered and phase separated, reminiscent of stress granule substructure or nanoscale liquid droplets.

Nanoscale thin-film flows with thermal fluctuations and slip.

The combined effects of thermal fluctuations and liquid-solid slip on nanoscale thin-film flows are investigated using stochastic lubrication equations (SLEs). The previous no-slip SLE for films on plates is extended to consider slip effects and a new SLE for films on fibers is derived, using a long-wave approximation to fluctuating hydrodynamics. Analytically derived capillary spectra, which evolve in time, are found from the new SLEs and compared to molecular dynamics simulations. It is shown that thermal fluctuations lead to the generation and growth of surface waves, and slip accelerates this growth. SLEs developed here provide useful tools to study nanoscale film dewetting, nanofiber coating, and liquid transport using nanofibers.