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1.
Nat Methods ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32203384

RESUMO

To image the accessible genome at nanometer scale in situ, we developed three-dimensional assay for transposase-accessible chromatin-photoactivated localization microscopy (3D ATAC-PALM) that integrates an assay for transposase-accessible chromatin with visualization, PALM super-resolution imaging and lattice light-sheet microscopy. Multiplexed with oligopaint DNA-fluorescence in situ hybridization (FISH), RNA-FISH and protein fluorescence, 3D ATAC-PALM connected microscopy and genomic data, revealing spatially segregated accessible chromatin domains (ACDs) that enclose active chromatin and transcribed genes. Using these methods to analyze genetically perturbed cells, we demonstrated that genome architectural protein CTCF prevents excessive clustering of accessible chromatin and decompacts ACDs. These results highlight 3D ATAC-PALM as a useful tool to probe the structure and organizing mechanism of the genome.

2.
Chemistry ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32154604

RESUMO

Here we report a novel and straightforward protocol for the construction of valuable gem -BPs by means of proton-coupled electron transfer (PCET)-triggered enamido C(sp 2 )-H diphosphorylation. This reaction represents a rare example of realizing the challenging double C-P bond formation at a same carbon atom, thus providing facile access to a broad variety of structurally diverse bisphosphonates from simple enamides under silver-mediated conditions. Initial mechanistic studies demonstrated that the diphosphorylation involves two rounds of PCET-initiated radical relay process.

3.
Oncol Lett ; 19(4): 2585-2594, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32218808

RESUMO

Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types.

4.
Photosynth Res ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152819

RESUMO

Zostera marina, a fully submerged marine angiosperm with a unique evolutionary history associated with its terrestrial origin, has distinct photochemical characteristics caused by its oxygen-evolving complex (OEC) being prone to deactivation in visible light. Based on the present phylogenetic analysis, the chloroplast NADPH dehydrogenase-like (NDH) complex was found to be completed in of Z. marina, unlike other marine plants, suggesting its crucial role. Thus, the responses of electron transport to irradiation were investigated through multiple chlorophyll fluorescence techniques and Western blot analysis. Moreover, the respective contribution of the two photosystem I cyclic electron flow (PSI-CEF) pathways to the generation of trans-thylakoid proton gradient (∆pH) was also examined using inhibitors. The contributions of the two PSI-CEF pathways to ∆pH were similar; furthermore, there was a trade-off between the two pathways under excess irradiation: the PGR5/L1-dependent PSI-CEF decreased gradually following its activation during the initial illumination, while NDH-dependent PSI-CEF was activated gradually with exposure duration. OEC inactivation was continuously under excess irradiation, which exhibits a positive linear correlation with the activation of NDH-dependent PSI-CEF. We suggest that PGR5/L1-dependent PSI-CEF was preferentially activated to handle the excess electron caused by the operation of OEC during the initial illumination. Subsequently, the increasing OEC inactivation with exposure duration resulted in a deficit of electrons. Limited electrons from PSI might preferentially synthesize NADPH, which could support the function of NDH-dependent PSI-CEF to generate ∆pH and ATP via reducing ferredoxin, thereby maintaining OEC stability.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32178876

RESUMO

C6-ceramide is an exogenous short-chain ceramide which can induce apoptosis of multiple cancer cells. Salivary adenoid cystic carcinoma (SACC) is a common salivary gland cancer, which possesses of high rate of local recurrence and distant metastasis. The mechanism of ceramide-induced SACC-83 and SACC-LM cell apoptosis has not been revealed. In our study, gene expression microarray was used to discover that the unfolded protein response (UPR) pathway, especially PRKR-like endoplasmic reticulum kinase (PERK) pathway, was the major activated pathway after treatment of c6-ceramide. D1ER, an endoplasmic-reticulum-targeted Ca2+ indicator, was used to measure Ca2+ release from endoplasmic reticulum (ER) dynamically. We found that inositol 1,4,5-trisphosphate receptor 3 (IP3R3) was activated, leading to Ca2+ release from ER, soon after c6-ceramide treatment. IP3R3 silencing could block UPR, although it could not prevent SACC-83 and SACC-LM cells from apoptosis. Moreover, we found that C/EBP-homologous protein could upregulate in a UPR-independent way. Mitochondria outer membrane permeabilization might play an important role in inducing SACC cell apoptosis.

6.
FEBS J ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129936

RESUMO

Anoikis (detachment-induced cell death) is a specific type of programmed cell death which occurs in response to the loss of the correct extracellular matrix connections. Anoikis resistance is an important mechanism in cancer invasiveness and metastatic behavior. Autophagy, on the other hand, involves the degradation of damaged organelles and the recycling of misfolded proteins and intracellular components. However, the intersection of these two cellular responses in lung cancer cells has not been extensively studied. Here, we identified that upon matrix deprivation, the lymphocyte lineage-specific Ets transcription factor SPIB was activated and directly enhanced SNAP47 transcription in certain lung cancer cells. Loss of attachment-induced autophagy significantly increased anoikis resistance by SPIB activation. Consistent with this function, SPIB depletion by short hairpin RNA abrogated SNAP47 transcriptional activation upon matrix deprivation. Therefore, these data delineate an important role of SPIB in autophagy-mediated anoikis resistance in lung cancer cells. Accordingly, these findings suggest that manipulating SPIB-regulated pathways in vivo and evaluating the impact of anoikis resistance warrant further investigation. DATABASE: RNA sequencing and ChIP sequencing data are available in Gene Expression Omnibus database under the accession numbers GSE106592 and GSE125561, respectively.

7.
J Cell Mol Med ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135028

RESUMO

Radiation protection on male testis is an important task for ionizing radiation-related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll-like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low-toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage-derived exosomes protein expression. We proved that after MPLA treatment, macrophage-derived exosomes played an important role in testis radiation protection, and specially, G-CSF and MIP-2 in exosomes are the core molecules in this protection effect.

8.
Magn Reson Med ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141644

RESUMO

PURPOSE: To develop a nonlinear preconditioned total field-inversion algorithm using the MEDI toolbox (MEDInpt) for robust QSM of carotid plaques and evaluate its performance in comparison with a local field-inversion algorithm (STI Suite) previously applied to carotid QSM. METHODS: Numerical simulation and in vivo carotid QSM were performed to compare the MEDInpt and STI Suite algorithms. Multicontrast MRI was used as the reference standard for detecting calcified plaque and intraplaque hemorrhage (IPH). A total of 5 healthy volunteers and 11 patients with at least one significant carotid artery stenosis were enrolled in this study. RESULTS: In the numerical carotid phantom, the relative susceptibility errors for calcified plaque and IPH were reduced from -63.2% and -56.5% with STI Suite to -13.0% and -24.2% with MEDInpt, respectively. In humans, MEDInpt provided a higher QSM quality score and better detection of calcification and IPH than STI Suite. Although all calcifications and IPHs detected on multicontrast MRI could be seen on QSM obtained with MEDInpt, only 50% of calcified plaques and 83% of IPHs could be captured on QSM obtained with STI Suite. CONCLUSION: MEDInpt can resolve calcification and IPH in advanced atherosclerotic carotid plaques. Compared with STI Suite, MEDInpt provided better QSM quality and has the potential to improve the detection of these plaque components.

9.
Proc Natl Acad Sci U S A ; 117(12): 6559-6570, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32156735

RESUMO

Secretagogin (SCGN) is a hexa-EF-hand protein that is highly expressed in the pancreas, brain, and gastrointestinal tract. SCGN is known to modulate regulated exocytosis in multiple cell lines and tissues; however, its exact functions and underlying mechanisms remain unclear. Here, we report that SCGN interacts with the plasma membrane SNARE SNAP-25, but not the assembled SNARE complex, in a Ca2+-dependent manner. The crystal structure of SCGN in complex with a SNAP-25 fragment reveals that SNAP-25 adopts a helical structure and binds to EF-hands 5 and 6 of SCGN. SCGN strongly inhibits SNARE-mediated vesicle fusion in vitro by binding to SNAP-25. SCGN promotes the plasma membrane localization of SNAP-25, but not Syntaxin-1a, in SCGN-expressing cells. Finally, SCGN controls neuronal growth and brain development in zebrafish, likely via interacting with SNAP-25 or its close homolog, SNAP-23. Our results thus provide insights into the regulation of SNAREs and suggest that aberrant synapse functions underlie multiple neurological disorders caused by SCGN deficiency.

10.
Gene ; 737: 144451, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035243

RESUMO

Cucumber mosaic virus (CMV) can cause serious losses in Luffa cylindrica (L.) Roem. Chemical application to control CMV is ineffective and environmentally unfriendly. The development of resistant hybrids is the best way to control CMV disease. Elucidating the virus-host interaction of CMV and molecular basis underlying Luffa spp. resistance against CMV would undoubtedly facilitate breeding for resistance against CMV disease. Transcriptome sequencing was used to analyze differentially expressed genes (DEGs) caused by CMV infection. A total of 138,336 unigenes were assembled, and 74,525 unigenes were annotated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the three major enrichment pathways (according to the p-values) were flavonoid biosynthesis, sulfur metabolism, and photosynthesis. Genes involved in basal defenses, probably R genes, were determined to be related to CMV resistance. Using quantitative real-time PCR, we validated the differential expression of 8 genes. A number of genes associated with CMV resistance were found in this study. This study provides transcriptomic information regarding CMV-Luffa spp. interactions and will shed light on our understanding of host-virus interactions.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32071011

RESUMO

Epilepsy is a chronic neurological disorder characterized by the occurrence of spontaneous seizures, which affects about one percent of the worlds population. Most of the current seizure detection approaches strongly rely on patient history records and thus fail in the patient-independent situation of detecting the new patients. To overcome such limitation, we propose a robust and explainable epileptic seizure detection model that effectively learns from seizure states while eliminates the inter-patient noises. A complex deep neural network model is proposed to learn the pure seizure-specific representation from the raw non-invasive electroencephalography (EEG) signals through adversarial training. Furthermore, to enhance the explainability, we develop an attention mechanism to automatically learn the importance of each EEG channels in the seizure diagnosis procedure. The proposed approach is evaluated over the Temple University Hospital EEG (TUH EEG) database. The experimental results illustrate that our model outperforms the competitive state-of-the-art baselines with low latency. Moreover, the designed attention mechanism is demonstrated ables to provide fine-grained information for pathological analysis. We propose an effective and efficient patient-independent diagnosis approach of epileptic seizure based on raw EEG signals without manually feature engineering, which is a step toward the development of large-scale deployment for real-life use.

12.
Chemistry ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073723

RESUMO

Electron-donor tetrathiafulvalene ( TTF , D 1 ) was fused onto the electron-rich hetera-buckybowl trichalcogenasumanene ( TCS , D 2 ) via an electron-deficient pyrazine unit (A) to give 1c , 1d , 2c , and 2d featuring D 1 -A-D 2 structure. Both D 1 and D 2 play pivotal role on intramolecular charge-transfer (ICT) transition, consequently 1c , d - 2 c, d show broad ICT band at 450-720 nm in steady-state. They exhibit two charge-separated transient states CS 1 and CS 2 that appear in sequence. CS 1 has a short lifetime (542 fs), and the D 1 moiety on CS 1 is in cation radical state with absorption maximum ( λ max ) at 889 nm. CS 1 then converts into CS 2 ( λ max , 1105 nm) via ICT between (D 1 ) +• and D 2 , affording (D 1 ) (1-δ)+• and (D 2 ) δ+• . The 1c , d - 2 c, d show protonation-induced intramolecular electron transfer that leads to absorption at 700-1300 nm. Owing to existence of electron-rich C=C bond on D 1 moiety and in-situ generation of 1 O 2 by pyrazine-fused TCS moiety, 1c , d - 2 c, d display self-sensitized photooxidation in 50s.

13.
Genes (Basel) ; 11(2)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041308

RESUMO

The rapid alkalinization factor (RALF) gene family is essential for the plant growth and development. However, there is little known about these genes among Rosaceae species. Here, we identify 124 RALF-like genes from seven Rosaceae species, and 39 genes from Arabidopsis, totally 163 genes, divided into four clades according to the phylogenetic analysis, which includes 45 mature RALF genes from Rosaceae species. The YISY motif and RRXL cleavage site are typical features of true RALF genes, but some variants were detected in our study, such as YISP, YIST, NISY, YINY, YIGY, YVGY, FIGY, YIAY, and RRVM. Motif1 is widely distributed among all the clades. According to screening of cis-regulatory elements, GO annotation, expression sequence tags (EST), RNA-seq, and RT-qPCR, we reported that 24 RALF genes coding mature proteins related to tissue development, fungal infection, and hormone response. Purifying selection may play an important role in the evolutionary process of RALF-like genes among Rosaceae species according to the result from ka/ks. The tandem duplication event just occurs in four gene pairs (Fv-RALF9 and Fv-RALF10, Md-RALF7 and Md-RALF8, Pm-RALF2 and Pm-RALF8, and Pp-RALF11 and Pp-RALF14) from four Rosaceae species. Our research provides a wide overview of RALF-like genes in seven Rosaceae species involved in identification, classification, structure, expression, and evolution analysis.

14.
Cancer Lett ; 475: 92-98, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32032678

RESUMO

Ultrasound associated with ultrasound contrast agents has witnessed ever-growing innovations and applications for disease-targeted diagnosis and therapy. With these state-of-the-art technologies, brand-new invasive or minimally invasive treatments are on the way to be clinically translated. This mini-review focuses on the ultrasound and ultrasound-related micro/nanobubbles as multifunctional agents for drug/gene delivery and multi-modality treatments, e.g. photodynamic, sonodynamic and photothermal therapies in a precise and visualized manner.

15.
Molecules ; 25(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019194

RESUMO

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

16.
Biosci Rep ; 40(2)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32031203

RESUMO

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high incidence and poor prognosis. Hypoxia and DNA methylation play important regulatory roles in cancer progression. The purpose of the present study was to explore the relationship between hypoxia and DNA methylation, and to identify key genes for hypoxia-regulated LUAD progression. Hypoxia score (HS) was calculated using the GSVA algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) analysis were performed using clusterProfile package, STRING database and Cytoscape software. Kaplan-Meier curves of overall survival (OS) and disease-free survival (DFS) were drawn using R software. Smoking status and cancer stages were significantly associated with LUAD hypoxia, and hypoxia is a poor prognostic factor for LUAD. Compared with HS-low group, 1803 aberrantly methylated DEGs were identified in HS-high group. KEGG analysis showed that the 1803 genes were enriched in the metabolic pathways associated with hypoxia stress, angiogenesis and cancer progression. FAM20C, MYLIP and COL7A1 were identified as the hypoxia-related key genes in LUAD progression, which were regulated by DNA methylation. Hypoxia in LUAD tumor cells led to changes in DNA methylation patterns. In-depth study of the relationship between hypoxia and DNA methylation is helpful to elucidate the mechanism of tumorigenesis, and provides new ideas for LUAD treatment.

17.
Turk J Med Sci ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32041384

RESUMO

BACKGROUND/AIM: This study aimed to investigate the correlation between the Glasgow-Blatchford score, shock index, and Forrest classification in patients with peptic ulcer bleeding. MATERIALS AND METHODS: A total of 955 patients with peptic ulcer bleeding were assessed using the Glasgow-Blatchford score and shock index, as well as the Forrest classification based on gastroscopic results. The correlation between the Glasgow-Blatchford score and shock index was determined using scatter plot analysis, and the correlation between the Glasgow-Blatchford score or shock index and Forrest classification was determined using Spearman?s analysis. RESULTS: Both the Glasgow-Blatchford score and shock index showed highest values in patients with Forrest class IIa. The Glasgow-Blatchford score was significantly higher than patients with Forrest class Ib/IIc/III (P<0.05), and the shock index was significantly higher than patients with Forrest class Ib/IIb/III (P<0.05). A positive correlation was observed between the Glasgow-Blatchford score and shock index, with r=0.427 (P<0.001). A negative correlation was observed between the Glasgow-Blatchford score and Forrest classification, with r=-0.111 (P<0.01), and between the shock index and Forrest classification, with r=-0.138 (P<0.01). CONCLUSIONS: A moderate correlation was observed between the Glasgow-Blatchford score and shock index in patients with peptic ulcer bleeding, and the correlation between Forrest classification and Glasgow-Blatchford score or shock index was relatively low.

18.
BMC Bioinformatics ; 21(1): 35, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000677

RESUMO

BACKGROUND: Automated biomedical named entity recognition and normalization serves as the basis for many downstream applications in information management. However, this task is challenging due to name variations and entity ambiguity. A biomedical entity may have multiple variants and a variant could denote several different entity identifiers. RESULTS: To remedy the above issues, we present a novel knowledge-enhanced system for protein/gene named entity recognition (PNER) and normalization (PNEN). On one hand, a large amount of entity name knowledge extracted from biomedical knowledge bases is used to recognize more entity variants. On the other hand, structural knowledge of entities is extracted and encoded as identifier (ID) embeddings, which are then used for better entity normalization. Moreover, deep contextualized word representations generated by pre-trained language models are also incorporated into our knowledge-enhanced system for modeling multi-sense information of entities. Experimental results on the BioCreative VI Bio-ID corpus show that our proposed knowledge-enhanced system achieves 0.871 F1-score for PNER and 0.445 F1-score for PNEN, respectively, leading to a new state-of-the-art performance. CONCLUSIONS: We propose a knowledge-enhanced system that combines both entity knowledge and deep contextualized word representations. Comparison results show that entity knowledge is beneficial to the PNER and PNEN task and can be well combined with contextualized information in our system for further improvement.

19.
Nanotechnology ; 31(23): 235501, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32069442

RESUMO

The fluorescence resonance energy transfer (FRET)-based diagnosis method has been widely used in fast and accurate diagnosis. However, the traditional FRET-based diagnosis method is unable to detect long-chain DNA sequences, due to the limitation of the distance between the donor and acceptor, while the long-chain DNA sequence enables higher selectivity and is quite important for confirming many major diseases. Therefore, it is urgently needed to develop an efficient FRET system for long-chain DNA detection. Herein a 'head-to-tail' structure was developed using NaYF4:Yb,Er nanoparticles as the energy donor and gold nanoparticles (AuNPs) as the acceptor to detect long-chain oligonucleotides sequences (i.e., HIV DNA, 52 bp). We modified NaYF4:Yb,Er nanoparticles with carboxylic acid groups by using poly(acrylic acid) to enhance its hydrophilic and then covalently attached 5 'end of capture oligonucleotides strand to the surface of the particles. In the presence of target HIV DNA, gold nanoparticles with reported DNA were brought close to NaYF4:Yb,Er nanoparticles upon 'head-to-tail' sandwich hybridization with target HIV DNA, resulting in an efficient FRET. Moreover, benefited from both photostable nanoparticles of UCNPs and AuNPs, the photobleaching issue has also been settled down. This developed method possesses high selectivity, high sensitivity, and reached a nanomolar limitation level. To our knowledge, it is the first time to report a 'head-to-tail' structure FRET system for detecting long-chain DNA sequences.

20.
Sci Rep ; 10(1): 478, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949206

RESUMO

We study the morphology of lipid membranes subjected to intra-membrane viscous flows and interactions with elliptical cylinder substrates. From the non-linear theory of elastic surfaces, a linearized shape equation and admissible boundary conditions are formulated in elliptical coordinates via the Monge representation of a surface. In particular, the intra-membrane viscosity terms are linearized and mapped into elliptic coordinates in order to accommodate more general forms of viscous flow. The assimilated viscous flow is characterized by potential functions which satisfies the continuity condition. A complete solution in terms of Mathieu function is then obtained within the prescription of incremental deformations superposed on large. The results describe smooth morphological transitions over the domain of interest and, more importantly, predicts wrinkle formations in the presence of intra-membrane viscous flow in the surface. Lastly, the obtained solution accommodates the results from the circular cases in the limit of vanishing eccentricity and intra-membrane viscous flow.

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