scholarly journals Efficient differentiation and polarization of primary cultured neurons on poly(lactic acid) scaffolds with microgrooved structures

2019 ◽  
Author(s):  
Asako Otomo ◽  
Mahoko Takahashi Ueda ◽  
Toshinori Fujie ◽  
Arihiro Hasebe ◽  
Yosuke Okamura ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Cell Adhesion ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Structural Features ◽  
Poly Lactic Acid ◽  
Adhesion Properties ◽  
Expression Of Genes ◽  
Cultured Cortical Neurons

AbstractSynthetic biodegradable polymers including poly(lactic acid) (PLA) are attractive cell culture substrates because their surfaces can be micropatterned to support cell adhesion. The cell adhesion properties of a scaffold mainly depend on its surface chemical and structural features; however, it remains unclear how these characteristics affect the growth and differentiation of cultured cells or their gene expression. In this study, we fabricated two differently structured PLA nanosheets: flat and microgrooved. We assessed the growth and differentiation of mouse primary cultured cortical neurons on these two types of nanosheets after pre-coating with poly-D-lysine and vitronectin. Interestingly, prominent neurite bundles were formed along the grooves on the microgrooved nanosheets, whereas thin and randomly extended neurites were only observed on the flat nanosheets. Comparative RNA sequencing analyses revealed that the expression of genes related to postsynaptic density, dendritic shafts, and asymmetric synapses was significantly and consistently up-regulated in cells cultured on the microgrooved nanosheets when compared with those cultured on the flat nanosheets. These results indicate that microgrooved PLA nanosheets can provide a powerful means of establishing a culture system for the efficient and reproducible differentiation of neurons, which will facilitate future investigations of the molecular mechanisms underlying the pathogenesis of neurological disorders.

Direct 3D Printing of Poly(lactic acid) on Cotton Fibers: Characterization of Materials and Study of Adhesion Properties of the Resulting Composites

2020 ◽  
Vol 394 (1) ◽  
pp. 1900190
Author(s):  
Franco Leonardo Redondo ◽  
María Carolina Giaroli ◽  
Marcelo Armando Villar ◽  
Augusto Gonzaga Oliveira Freitas ◽  
Andrés Eduardo Ciolino ◽  
...  
Keyword(s):  
Lactic Acid ◽  
3D Printing ◽  
Cotton Fibers ◽  
Poly Lactic Acid ◽  
Adhesion Properties ◽  
Characterization Of Materials

scholarly journals Effect of nano-hydroxyapatite on protein adsorption and cell adhesion of poly(lactic acid)/nano-hydroxyapatite composite microspheres

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
H. M. C. Suboda Wijerathne ◽  
Dong Yan ◽  
Bin Zeng ◽  
Yanping Xie ◽  
Hongchao Hu ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Cell Adhesion ◽  
Protein Adsorption ◽  
Poly Lactic Acid ◽  
Composite Microspheres ◽  
Hydroxyapatite Composite

scholarly journals Grafting collagen on poly (lactic acid) by a simple route to produce electrospun scaffolds, and their cell adhesion evaluation

2016 ◽  
Vol 13 (4) ◽  
pp. 375-387 ◽  
Author(s):  
Alida Ospina-Orejarena ◽  
Ricardo Vera-Graziano ◽  
Maria Monica Castillo-Ortega ◽  
Juan Paulo Hinestroza ◽  
Mabel Rodriguez-Gonzalez ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Cell Adhesion ◽  
Poly Lactic Acid ◽  
Simple Route ◽  
Electrospun Scaffolds

scholarly journals Atomic-level characterization and cilostazol affinity of poly(lactic acid) nanoparticles conjugated with differentially charged hydrophilic molecules

2018 ◽  
Vol 9 ◽  
pp. 1328-1338 ◽  
Author(s):  
María Francisca Matus ◽  
Martín Ludueña ◽  
Cristian Vilos ◽  
Iván Palomo ◽  
Marcelo M Mariscal
Keyword(s):  
Lactic Acid ◽  
Rational Design ◽  
Drug Loading ◽  
Surface Region ◽  
Structural Features ◽  
Modern Medicine ◽  
Poly Lactic Acid ◽  
Surface Design ◽  
Key Factor ◽  
Full Picture

Nanotherapeutics is a promising field for numerous diseases and represents the forefront of modern medicine. In the present work, full atomistic computer simulations were applied to study poly(lactic acid) (PLA) nanoparticles conjugated with polyethylene glycol (PEG). The formation of this complex system was simulated using the reactive polarizable force field (ReaxFF). A full picture of the morphology, charge and functional group distribution is given. We found that all terminal groups (carboxylic acid, methoxy and amino) are randomly distributed at the surface of the nanoparticles. The surface design of NPs requires that the charged groups must surround the surface region for an optimal functionalization/charge distribution, which is a key factor in determining physicochemical interactions with different biological molecules inside the organism. Another important point that was investigated was the encapsulation of drugs in these nanocarriers and the prediction of the polymer–drug interactions, which provided a better insight into structural features that could affect the effectiveness of drug loading. We employed blind docking to predict NP–drug affinity testing on an antiaggregant compound, cilostazol. The results suggest that the combination of molecular dynamics ReaxFF simulations and blind docking techniques can be used as an explorative tool prior to experiments, which is useful for rational design of new drug delivery systems.

scholarly journals Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion

2020 ◽  
Author(s):  
Sina Ibne Noor ◽  
Marcus Hoffmann ◽  
Natalie Rinis ◽  
Markus F. Bartels ◽  
Patrick Winterhalter ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Adhesion Properties ◽  
Knock Out ◽  
Mesenchymal Transition ◽  
Transcriptional Changes ◽  
Cell Cell

AbstractDefects in protein O-mannosylation lead to severe congenital muscular dystrophies known as α-dystroglycanopathy. A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which leads to a reduction in cell adhesion to the extracellular matrix. Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, are mainly associated with muscle-eye-brain (MEB) disease. In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1. However, direct molecular mechanisms are largely unknown. We used POMGNT1 knock-out HEK293T cells and fibroblasts from a MEB patient to gain a deeper insight into the molecular changes in POMGNT1 deficiency. A combination of biochemical and molecular biological techniques with proteomics, glycoproteomics and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion. We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh). In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions. We found that in POMGNT1 deficient cells ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable to the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype. Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general, and suggests a previously underestimated impact of changes in O-mannosylation on N-glycosylation.

Diamond nanoparticles into poly (lactic acid) electrospun fibers: Cytocompatible and bioactive scaffolds with enhanced wettability and cell adhesion

2016 ◽  
Vol 183 ◽  
pp. 420-424 ◽  
Author(s):  
F.A.S. Pereira ◽  
G.N. Salles ◽  
B.V.M. Rodrigues ◽  
F.R. Marciano ◽  
C. Pacheco-Soares ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Cell Adhesion ◽  
Poly Lactic Acid ◽  
Electrospun Fibers ◽  
Diamond Nanoparticles ◽  
Bioactive Scaffolds

scholarly journals Protein Kinase KIS Localizes to RNA Granules and Enhances Local Translation

2008 ◽  
Vol 29 (3) ◽  
pp. 726-735 ◽  
Author(s):  
Serafí Cambray ◽  
Neus Pedraza ◽  
Marta Rafel ◽  
Eloi Garí ◽  
Martí Aldea ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Local Translation ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Rna Granules ◽  
Axon Development ◽  
Brain Extracts ◽  
Cultured Cortical Neurons ◽  
Actin Mrna

ABSTRACT The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the β-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3′ untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.

scholarly journals Molecular Dynamics Studies of Poly(Lactic Acid) Nanoparticles and Their Interactions with Vitamin E and TLR Agonists Pam1CSK4 and Pam3CSK4

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2209
Author(s):  
Simon Megy ◽  
Stephanie Aguero ◽  
David Da Costa ◽  
Myriam Lamrayah ◽  
Morgane Berthet ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Vitamin E ◽  
Molecular Mechanisms ◽  
Drug Carrier ◽  
Rapid Development ◽  
Dissipative Particle Dynamics ◽  
New Drugs ◽  
Poly Lactic Acid ◽  
Biologically Relevant ◽  
Tlr Agonists

Poly(lactic acid) (PLA) nanoparticles (NPs) are widely investigated due to their bioresorbable, biocompatible and low immunogen properties. Interestingly, many recent studies show that they can be efficiently used as drug delivery systems or as adjuvants to enhance vaccine efficacy. Our work focuses on the molecular mechanisms involved during the nanoprecipitation of PLA NPs from concentrated solutions of lactic acid polymeric chains, and their specific interactions with biologically relevant molecules. In this study, we evaluated the ability of a PLA-based nanoparticle drug carrier to vectorize either vitamin E or the Toll-like receptor (TLR) agonists Pam1CSK4 and Pam3CSK4, which are potent activators of the proinflammatory transcription factor NF-κB. We used dissipative particle dynamics (DPD) to simulate large systems mimicking the nanoprecipitation process for a complete NP. Our results evidenced that after the NP formation, Pam1CSK4 and Pam3CSK4 molecules end up located on the surface of the particle, interacting with the PLA chains via their fatty acid chains, whereas vitamin E molecules are buried deeper in the core of the particle. Our results allow for a better understanding of the molecular mechanisms responsible for the formation of the PLA NPs and their interactions with biological molecules located either on their surfaces or encapsulated within them. This work should allow for a rapid development of better biodegradable and safe vectorization systems with new drugs in the near future.

scholarly journals Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a

2020 ◽  
Author(s):  
Xing-Lei Song ◽  
Di-Shi Liu ◽  
Min Qiang ◽  
Qian Li ◽  
Ming-Gang Liu ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Membrane Surface ◽  
Single Particle Tracking ◽  
Synaptic Activity ◽  
Long Distance ◽  
Synaptic Functions ◽  
Cultured Cortical Neurons ◽  
The Central Nervous System ◽  
High Dynamics

Abstract Acid-sensing ion channels (ASICs), the main H+ receptors in the central nervous system, sense extracellular pH fluctuations and mediate cation influx. ASIC1a, the major subunit responsible for acid-activated current, is widely expressed in brain neurons, where it plays pivotal roles in diverse functions including synaptic transmission and plasticity. However, the underlying molecular mechanisms for these functions remain mysterious. Using extracellular epitope tagging and a novel antibody recognizing the hASIC1a ectodomain, we examined the membrane targeting and dynamic trafficking of hASIC1a in cultured cortical neurons. Surface hASIC1a was distributed throughout somata and dendrites, clustered in spine heads, and co-localized with postsynaptic markers. By extracellular pHluorin tagging and fluorescence recovery after photobleaching, we detected movement of hASIC1a in synaptic spine heads. Single-particle tracking along with use of the anti-hASIC1a ectodomain antibody revealed long-distance migration and local movement of surface hASIC1a puncta on dendrites. Importantly, enhancing synaptic activity with brain-derived neurotrophic factor accelerated the trafficking and lateral mobility of hASIC1a. With this newly-developed toolbox, our data demonstrate the synaptic location and high dynamics of functionally-relevant hASIC1a on the surface of excitatory synapses, supporting its involvement in synaptic functions.

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