Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual mechanism ?-amino acid polymers promoting cell adhesion.

ABSTRACT: Cell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic amphiphilic ?-amino acid polymers that are stable upon proteolysis and easily prepared in large scale at low cost. The optimal polymer strongly promotes cell adhesion, using preosteoblast cell as a model, by following dual mechanisms that are independent of sequence and chirality of the statistic copolymer. Our strategy opens avenues in designing the next-generation cell-adhesive materials and may guide future studies and applications.

SUBMITTER: Chen Q

PROVIDER: S-EPMC7835237 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dual mechanism β-amino acid polymers promoting cell adhesion.

Chen Qi Q Zhang Donghui D Zhang Wenjing W Zhang Haodong H Zou Jingcheng J Chen Mingjiao M Li Jin J Yuan Yuan Y Liu Runhui R

Nature communications 20210125 1

Cell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic am ...[more]

PMID: 33495467

Similar Datasets

Amino acid-bearing ROMP polymers with a stereoregular backbone.

Project description:The ruthenium-catalyzed ring-opening polymerization (ROMP) of 1-cyclobutenecarbonyl glycine methyl ester provides translationally invariant, head-to-tail ordered polymers. This polybutadiene backbone contains (within the limits of detection) only E-trisubstituted olefins, and it has no stereocenters that would serve as a source of structural ambiguities. Characterization of the polymer products indicates that they have polydispersities ranging from 1.2 to 1.6 and suggests that they are the products of a "living" polymerization. 1-Cyclobutenecarboxamide-derived ROMP polymers are excellent prospects for applications that require stereoregular chains functionalized with polar ligands.

| S-EPMC2562595 | biostudies-literature

Structural Transformations of Amino-Acid-Based Polymers: Syntheses and Structural Characterization.

Project description:A discrete complex [Zn(tpro)₂(H₂O)₂] (1, Htpro = l-thioproline), and two structural isomers of coordination polymers, a 1D chain of [Zn(tpro)₂]n (2) and a layered structure [Zn(tpro)₂]n (3), were synthesized and characterized. The discrete complex 1 undergoes a temperature-driven structural transformation, leading to the formation of a 1D helical coordination polymer 2. Compound 3 is comprised of a 2D homochiral layer network with a (4,4) topology. These layers are mutually linked through hydrogen bonding interactions, resulting in the formation of a 3D network. When 1 is heated, it undergoes nearly complete conversion to the microcrystalline form, i.e., compound 2, which was confirmed by powder X-ray diffractions (PXRD). The carboxylate motifs could be activated after removing the coordinated water molecules by heating at temperatures of up to 150 °C, their orientations becoming distorted, after which, they attacked the activation sites of the Zn(II) centers, leading to the formation of a 1D helix. Moreover, a portion of the PXRD pattern of 1 was converted into the patterns corresponding to 2 and 3, and the ratio between 2 and 3 was precisely determined by the simulation study of in-situ synchrotron PXRD expriments. Consequently, such a 0D complex is capable of underdoing structural transformations and can be converted into 1D and/or 2D amino acid-based coordination polymers.

| S-EPMC6414969 | biostudies-literature

Exploring the mechanism of beta-amyloid toxicity attenuation by multivalent sialic acid polymers through the use of mathematical models.

Project description:beta-Amyloid peptide (A beta), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the A beta-neuronal membrane interaction plays a role in the mechanism of A beta toxicity. More specifically, it is thought that A beta interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have used a number of different sialic acid compounds of different valency or number of sialic acid moieties per molecule to attenuate A beta toxicity in a cell culture model. In this work, we proposed various mathematical models of A beta interaction with both the cell membrane and with the multivalent sialic acid compounds, designed to act as membrane mimics. These models allow us to explore the mechanism of action of this class of sialic acid membrane mimics in attenuating the toxicity of A beta. The mathematical models, when compared with experimental data, facilitate the discrimination between different modes of action of these materials. Understanding the mechanism of action of A beta toxicity inhibitors should provide insight into the design of the next generation of molecules that could be used to prevent A beta toxicity associated with AD.

| S-EPMC2755187 | biostudies-literature

GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels.

Project description:EIF2AK4, which encodes the amino acid deficiency-sensing protein GCN2, has been implicated as a susceptibility gene for type 2 diabetes in the Japanese population. However, the mechanism by which GCN2 affects glucose homeostasis is unclear. Here, we show that insulin secretion is reduced in individuals harboring the risk allele of EIF2AK4 and that maintenance of GCN2-deficient mice on a high-fat diet results in a loss of pancreatic β cell mass. Our data suggest that GCN2 senses amino acid deficiency in β cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent β cell failure during the consumption of a high-fat diet.

| S-EPMC7253016 | biostudies-literature

α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism.

Project description:The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian αE-catenin (also known as catenin α-1) and Drosophila α-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of α-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal α-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of α-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of α-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the α-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

| S-EPMC4359922 | biostudies-literature

Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action.

Project description:BackgroundChronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.MethodsNIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.ResultsWe found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.ConclusionThis study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.

| S-EPMC6943256 | biostudies-literature

Side-Chain Amino Acid-Based Cationic Antibacterial Polymers: Investigating the Morphological Switching of a Polymer-Treated Bacterial Cell.

Project description:Synthetic polymer-based antimicrobial materials destroy conventional antibiotic resistant microorganisms. Although these antibacterial polymers imitate the properties of antimicrobial peptides (AMPs), their effect on bacterial cell morphology has not been studied in detail. To investigate the morphology change of a bacterial cell in the presence of antimicrobial polymer, herein we have designed and synthesized side-chain amino acid-based cationic polymers, which showed efficient antibacterial activity against Gram-negative (Escherichia coli), as well as Gram-positive (Bacillus subtilis) bacteria. Morphological switching from a rod shape to a spherical shape of E. coli cells was observed by field emission-scanning electron microscopy analysis due to cell wall disruption, whereas the B. subtilis cell structure and size remained intact, but stacks of the cells formed after polymer treatment. The zone of inhibition experiment on an agar plate for E. coli cells exhibited drastic morphological changes at the vicinity of the polymer-treated portion and somewhat less of an effect at the periphery of the plate.

| S-EPMC6044850 | biostudies-literature

Carboxybetaine methacrylate polymers offer robust, long-term protection against cell adhesion.

Project description:Films of poly(carboxybetaine methacrylate), poly(CBMA), grafted onto microetched gold slides are effective in preventing nonspecific adhesion of cells of different types. The degree of adhesion resistance is comparable to that achieved with the self-assembled monolayers, SAMs, of oligo(ethylene glycol) alkanethiolates. In sharp contrast to the SAMs, however, substrates protected with poly(CBMA) can be stored in dry state without losing their protective properties for periods up to 2 weeks.

| S-EPMC3597224 | biostudies-literature

Cell type specific adhesion to surfaces functionalised by amine plasma polymers.

Project description:Our previously-obtained impressive results of highly increased C2C12 mouse myoblast adhesion to amine plasma polymers (PPs) motivated current detailed studies of cell resistance to trypsinization, cell proliferation, motility, and the rate of attachment carried out for fibroblasts (LF), keratinocytes (HaCaT), rat vascular smooth muscle cells (VSMC), and endothelial cells (HUVEC, HSVEC, and CPAE) on three different amine PPs. We demonstrated the striking difference in the resistance to trypsin treatment between endothelial and non-endothelial cells. The increased resistance observed for the non-endothelial cell types was accompanied by an increased rate of cellular attachment, even though spontaneous migration was comparable to the control, i.e., to the standard cultivation surface. As demonstrated on LF fibroblasts, the resistance to trypsin was similar in serum-supplemented and serum-free media, i.e., medium without cell adhesion-mediating proteins. The increased cell adhesion was also confirmed for LF cells by an independent technique, single-cell force spectroscopy. This method, as well as the cell attachment rate, proved the difference among the plasma polymers with different amounts of amine groups, but other investigated techniques could not reveal the differences in the cell behaviour on different amine PPs. Based on all the results, the increased resistance to trypsinization of C2C12, LF, HaCaT, and VSMC cells on amine PPs can be explained most probably by a non-specific cell adhesion such as electrostatic interaction between the cells and amine groups on the material surface, rather than by the receptor-mediated adhesion through serum-derived proteins adsorbed on the PPs.

| S-EPMC7283471 | biostudies-literature

The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism.

Project description:Breast tumours are embedded in a collagen I-rich extracellular matrix (ECM) network, where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required macropinocytosis-dependent ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the up-regulation of the intracellular levels of several amino acids, most notably tyrosine and phenylalanine. This resulted in elevated tyrosine catabolism on ECM under starvation, leading to increased fumarate levels, potentially feeding into the tricarboxylic acid (TCA) cycle. Interestingly, this pathway was required for ECM-dependent cell growth and invasive cell migration under amino acid starvation, as the knockdown of p-hydroxyphenylpyruvate hydroxylase-like protein (HPDL), the third enzyme of the pathway, opposed cell growth and motility on ECM in both 2D and 3D systems, without affecting cell proliferation on plastic. Finally, high HPDL expression correlated with poor prognosis in breast cancer patients. Collectively, our results highlight that the ECM in the tumour microenvironment (TME) represents an alternative source of nutrients to support cancer cell growth by regulating phenylalanine and tyrosine metabolism.

| S-EPMC10791009 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data