scholarly journals Study of interactions between polymer nanoparticles and cell membranes at atomistic levels

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140036 ◽  
Author(s):  
Chin W. Yong
Keyword(s):  
Cell Membranes ◽  
Membrane Surface ◽  
Animal Health ◽  
Md Simulations ◽  
Industrial Applications ◽  
Polymer Nanoparticles ◽  
Head Groups ◽  
Structure Of Nanoparticles ◽  
Hydrocarbon Chains ◽  
Modelling Techniques

Knowledge of how the structure of nanoparticles and the interactions with biological cell membranes is important not only for understanding nanotoxicological effects on human, animal health and the environment, but also for better understanding of nanoparticle fabrication for biomedical applications. In this work, we use molecular modelling techniques, namely molecular dynamics (MD) simulations, to explore how polymer nanoparticles interact with 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) lipid cell membranes. Two different polymers have been considered: 100 monomer units of polyethylene (approx. 2.83 kDa) and polystyrene (approx. 10.4 kDa), both of which have wide industrial applications. We found that, despite the polar lipid head groups acting as an effective barrier to prevent the nanoparticles from interacting with the membrane surface, irreversible adhesion can be initiated by insertion of dangling chain ends from the polymer into the hydrophobic interior of the membrane. In addition, alignment of chain segments from the polymers with that of hydrocarbon chains in the interior of the membrane facilitates the complete immersion of the nanoparticles into the cell membrane. These findings highlight the importance of the surface and the topological structures of the polymer particles that dictate the absorption behaviour into the membrane and, subsequently, induce the possible translocation into the cell.

The penetration of Human Defensin 5 (HD5) through bacterial outer membrane: Simulation studies

2021 ◽  
Author(s):  
Tadsanee Awang ◽  
Prapasiri Pongprayoon
Keyword(s):  
Pathogenic Bacteria ◽  
Lipid A ◽  
Dominant Role ◽  
Membrane Surface ◽  
Innate Immune ◽  
Hydrophobic Core ◽  
Gram Negative ◽  
Head Groups ◽  
Bacterial Outer Membrane ◽  
Human Defensin 5

Abstract Human α-defensin 5 (HD5) is one of cationic antimicrobial peptides which plays a crucial role in an innate immune system in human body. HD5 shows the killing activity against a broad spectrum of pathogenic bacteria by making a pore in a bacterial membrane and penetrating into a cytosol. Nonetheless, its pore-forming mechanisms remain unclear. Thus, in this work, the constant-velocity steered molecular dynamics (SMD) simulation was used to simulate the permeation of a dimeric HD5 into a gram-negative LPS membrane model. Arginine-rich HD5 is found to strongly interact with a LPS surface. Upon arrival, arginines on HD5 interact with lipid A head groups and then drag these charged moieties down into a hydrophobic core resulting in the formation of water-filled pore. Although all arginines are found to interact with a membrane, R13 and R32 appear to play a dominant role in the HD5 adsorption on a gram-negative membrane. Furthermore, one chain of a dimeric HD5 is required for HD5 adhesion. The interactions of arginine-Lipid A head groups play a major role in adhering a cationic HD5 on a membrane surface and retarding a HD5 passage in the meantime.

scholarly journals The search for new amphiphiles: synthesis of a modular, high-throughput library

2014 ◽  
Vol 10 ◽  
pp. 1578-1588 ◽  
Author(s):  
George C Feast ◽  
Thomas Lepitre ◽  
Xavier Mulet ◽  
Charlotte E Conn ◽  
Oliver E Hutt ◽  
...  
Keyword(s):  
High Throughput ◽  
Crystalline Phase ◽  
Liquid Crystalline ◽  
Phase Behaviour ◽  
Liquid Crystalline Phase ◽  
Preliminary Assessment ◽  
Degree Of Unsaturation ◽  
Amphiphilic Compounds ◽  
Head Groups ◽  
Hydrocarbon Chains

Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.

scholarly journals Insights into the Polyhexamethylene Biguanide (PHMB) Mechanism of Action on Bacterial Membrane and DNA: A Molecular Dynamics Study

2020 ◽  
Author(s):  
Shahin Sowlati-Hashjin ◽  
Paola Carbone ◽  
Mikko Karttunen
Keyword(s):  
Molecular Dynamics ◽  
Electrostatic Interactions ◽  
Membrane Surface ◽  
Md Simulations ◽  
Phospholipid Bilayer ◽  
Phospholipid Membrane ◽  
Replication Process ◽  
Polyhexamethylene Biguanide ◽  
Phosphate Backbone ◽  
Pass Through

AbstractPolyhexamethylene biguanide (PHMB) is a cationic polymer with antimicrobial and antiviral properties. It has been commonly accepted that the antimicrobial activity is due the ability of PHMB to perforate the bacterial phospholipid membrane leading ultimately to its death. In this study we show by the means of atomistic molecular dynamics (MD) simulations that while the PHMB molecules attach to the surface of the phospholipid bilayer and partially penetrate it, they do not cause any pore formation at least within the microsecond simulation times. The polymers initially adsorb onto the membrane surface via the favourable electrostatic interactions between the phospholipid headgroups and the biguanide groups, and then partially penetrate the membrane slightly disrupting its structure. This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively ‘bind’ to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways.TOC Graphic

scholarly journals The Role of a Crystallographically Unresolved Cytoplasmic Loop in Stabilizing the Bacterial Membrane Insertase YidC2

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thomas Harkey ◽  
Vivek Govind Kumar ◽  
Jeevapani Hettige ◽  
Seyed Hamid Tabari ◽  
Kalyan Immadisetty ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Structural Dynamics ◽  
Md Simulations ◽  
Protein Assembly ◽  
Bacillus Halodurans ◽  
Bacterial Membrane ◽  
Apparent Lack ◽  
Head Groups ◽  
Cytoplasmic Loops

Abstract YidC, a bacterial member of the YidC/Alb3/Oxa1 insertase family, mediates membrane protein assembly and insertion. Cytoplasmic loops are known to have functional significance in membrane proteins such as YidC. Employing microsecond-level molecular dynamics (MD) simulations, we show that the crystallographically unresolved C2 loop plays a crucial role in the structural dynamics of Bacillus halodurans YidC2. We have modeled the C2 loop and used all- atom MD simulations to investigate the structural dynamics of YidC2 in its apo form, both with and without the C2 loop. The C2 loop was found to stabilize the entire protein and particularly the C1 region. C2 was also found to stabilize the alpha-helical character of the C-terminal region. Interestingly, the highly polar or charged lipid head groups of the simulated membranes were found to interact with and stabilize the C2 loop. These findings demonstrate that the crystallographically unresolved loops of membrane proteins could be important for the stabilization of the protein despite the apparent lack of structure, which could be due to the absence of the relevant lipids to stabilize them in crystallographic conditions.

Spectroscopic studies of phospholamban variants in phospholipid bilayers

2005 ◽  
Vol 33 (5) ◽  
pp. 913-915 ◽  
Author(s):  
J.C. Clayton ◽  
E. Hughes ◽  
D.A. Middleton
Keyword(s):  
Calcium Ions ◽  
Transmembrane Protein ◽  
Membrane Surface ◽  
Cytoplasmic Domain ◽  
Spectroscopic Studies ◽  
Phospholipid Bilayers ◽  
Random Coil ◽  
Helical Conformation ◽  
Conformational Switch ◽  
Head Groups

Phospholamban (PLB) is a 52 amino acid transmembrane protein found in the sarcoplasmic reticulum of cardiac myocytes, where it regulates the transport of calcium ions by SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase). This work has shown that the cytoplasmic domain of PLB associates with phospholipid vesicles, possibly with the lipid polar head groups, and, in doing so, undergoes a transition from a random coil to a more helical conformation. These findings support a recent hypothesis that the cytoplasmic domain of PLB acts as a conformational switch, alternating between an orientation that lies across the membrane surface and an upright orientation that associates with the regulatory site of SERCA.

scholarly journals Flavonoid-membrane Interactions: A Protective Role of Flavonoids at the Membrane Surface?

2005 ◽  
Vol 12 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Patricia I. Oteiza ◽  
Alejandra G. Erlejman ◽  
Sandra V. Verstraeten ◽  
Carl L. Keen ◽  
César G. Fraga
Keyword(s):  
Membrane Surface ◽  
Polar Compounds ◽  
Protective Role ◽  
Membrane Lipid ◽  
Hydrophobic Core ◽  
Head Groups ◽  
Lipid And Protein Oxidation ◽  
Chain Breaking ◽  
A Chain ◽  
And Function

Flavonoids can exert beneficial health effects through multiple mechanisms. In this paper, we address the important, although not fully understood, capacity of flavonoids to interact with cell membranes. The interactions of polyphenols with bilayers include: (a) the partition of the more non-polar compounds in the hydrophobic interior of the membrane, and (b) the formation of hydrogen bonds between the polar head groups of lipids and the more hydrophilic flavonoids at the membrane interface. The consequences of these interactions are discussed. The induction of changes in membrane physical properties can affect the rates of membrane lipid and protein oxidation. The partition of certain flavonoids in the hydrophobic core can result in a chain breaking antioxidant activity. We suggest that interactions of polyphenols at the surface of bilayers through hydrogen bonding, can act to reduce the access of deleterious molecules (i.e. oxidants), thus protecting the structure and function of membranes.

scholarly journals Association of gelsolin with actin filaments and cell membranes of macrophages and platelets.

1989 ◽  
Vol 108 (2) ◽  
pp. 467-479 ◽  
Author(s):  
J H Hartwig ◽  
K A Chambers ◽  
T P Stossel
Keyword(s):  
Actin Filaments ◽  
Cell Membranes ◽  
Blood Platelets ◽  
Membrane Surface ◽  
Resting Cells ◽  
Thin Sections ◽  
Plasma Gelsolin ◽  
Freeze Dried ◽  
Secondary Lysosomes

Recent evidence that polyphosphoinositides regulate the function of the actin-modulating protein gelsolin in vitro raises the possibility that gelsolin interacts with cell membranes. This paper reports ultrastructural immunohistochemical data revealing that gelsolin molecules localize with plasma and intracellular membranes, including rough endoplasmic reticulum, cortical vesicles and mitochondria of macrophages, and blood platelets. Anti-gelsolin gold also labeled the surface and interior of secondary lysosomes presumably representing plasma gelsolin ingested by these cells from the lung surface by endocytosis. Gelsolin molecules, visualized with colloidal gold in replicas of the cytoplasmic side of the substrate-adherent plasma membrane of mechanically unroofed and rapidly frozen and freeze-dried macrophages, associated with the ends of short actin filaments sitting on the cytoplasmic membrane surface. A generalized distribution of gelsolin molecules in thin sections of resting platelets rapidly became peripheral, and plasmalemma association increased following thrombin stimulation. At later times the distribution reverted to the cytoplasmic distribution of resting cells. These findings provide the first evidence for gelsolin binding to actin filament ends in cells and indicate that gelsolin functions in both cytoplasmic and membrane domains.

scholarly journals Characterization and Functional Test of Canine Probiotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyun-Jun Jang ◽  
Seungwoo Son ◽  
Jung-Ae Kim ◽  
Min Young Jung ◽  
Yeon-jae Choi ◽  
...  
Keyword(s):  
Animal Health ◽  
Clinical Results ◽  
Industrial Applications ◽  
Bacterial Strains ◽  
Host Animal ◽  
Microbial Composition ◽  
Beneficial Effects ◽  
Acid And Bile Tolerance

Probiotics can modulate the composition of gut microbiota and benefit the host animal health in multiple ways. Lactic acid bacteria (LAB), mainly Lactobacillus and Bifidobacterium species, are well-known microbes with probiotic potential. In the present study, 88 microbial strains were isolated from canine feces and annotated. Among these, the four strains CACC517, 537, 558, and 566 were tested for probiotic characteristics, and their beneficial effects on hosts were evaluated both in vitro and in vivo; these strains exhibited antibiosis, antibiotic activity, acid and bile tolerance, and relative cell adhesion to the HT-29 monolayer cell line. Byproducts of these strains increased the viability and decreased oxidative stress in mouse and dog cell lines (RAW264.7 and DH82, respectively). Subsequently, when the probiotics were applied to the clinical trial, changes in microbial composition and relative abundance of bacterial strains were clearly observed in the experimental animals. Experimental groups before and after the application were obviously separated from PCA analysis of clinical results. Conclusively, these results could provide comprehensive understanding of the effects of probiotic strains (CACC517, 537, 558, and 566) and their industrial applications.

Sign in / Sign up

Export Citation Format

Share Document