scholarly journals Asymmetric phospholipids impart novel biophysical properties to lipid bilayers allowing environmental adaptation

2020 ◽  
Author(s):  
Paul Smith ◽  
Dylan M. Owen ◽  
Christian D. Lorenz ◽  
Maria Makarova
Keyword(s):  
Lipid Bilayers ◽  
Mammalian Cells ◽  
Yeast Species ◽  
Membrane Lipid ◽  
Head Group ◽  
Biophysical Properties ◽  
Biophysical Parameters ◽  
Unsaturated Lipids ◽  
Chain Acyl ◽  
Dynamics Simulations

AbstractPhospholipids are a diverse group of biomolecules consisting of a hydrophilic head group and two hydrophobic acyl tails. The nature of the head and length and saturation of the acyl tails are important for defining the biophysical properties of lipid bilayers. It has recently been shown that the membranes of certain yeast species contain high levels of unusual asymmetric phospholipids, consisting of one long and one medium chain acyl moiety – a configuration not common in mammalian cells or other well studied model yeast species. This raises the possibility that structurally asymmetric phospholipids impart novel biophysical properties to the yeast membranes. Here, we use atomistic molecular dynamics simulations (MD) and environmentally-sensitive fluorescent membrane probes to characterize key biophysical parameters of membranes formed from asymmetric lipids for the first time. Interestingly, we show that saturated, but asymmetric phospholipids maintain membrane lipid order across a wider range of temperatures and do not require acyl tail unsaturation or sterols to maintain their properties. This may allow cells to maintain membrane fluidity even in environments which lack the oxygen required for the synthesis of unsaturated lipids and sterols.

scholarly journals Composition fluctuations in lipid bilayers

2016 ◽  
Author(s):  
Svetlana Baoukina ◽  
Dmitri Rozmanov ◽  
D. Peter Tieleman
Keyword(s):  
Lipid Bilayers ◽  
Liquid Crystalline ◽  
Dynamic Properties ◽  
Coarse Grained ◽  
Gradual Transition ◽  
Dynamic Heterogeneity ◽  
Two Phase ◽  
Unsaturated Lipids ◽  
Dynamics Simulations ◽  
Composition Fluctuations

AbstractLipid bilayers constitute the basis of biological membranes. Understanding lipid mixing and phase behavior can provide important insights into membrane lateral organization (the “raft” hypothesis). Here we investigate model lipid bilayers below and above their miscibility transition temperatures. Molecular dynamics simulations with the MARTINI coarse-grained force field are employed to model bilayers on a length scale approaching 100 nm and a time scale of tens of microseconds. Using a binary mixture of saturated and unsaturated lipids, and a ternary mixture of a saturated lipid, an unsaturated lipid and cholesterol we reproduce the coexistence of liquid-crystalline and gel, as well as liquid-ordered and liquid-disordered phases. By raising the temperature or adding hybrid lipids (with a saturated and an unsaturated chain), we induce a gradual transition from a two-phase to a one-phase state. We characterize the evolution of bilayer properties along this transition. Domains of coexisting phases change to dynamic heterogeneity with local ordering and compositional de-mixing. We analyze the structural and dynamic properties of domains, sizes and lifetimes of composition fluctuations, and calculate the in-plane structure factors.

Study on Molecular Thermal Energy Transfer in a Lipid Bilayer

2007 ◽  
Author(s):  
Takeo Nakano ◽  
Taku Ohara ◽  
Gota Kikugawa
Keyword(s):  
Energy Transfer ◽  
Thermal Resistance ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Thermal Energy ◽  
Hydrocarbon Chain ◽  
Bilayer Membrane ◽  
Head Group ◽  
Total Thermal Resistance ◽  
Dynamics Simulations

In recent studies, lipid bilayers attract a great deal of interest as a material for nanoscale structure. Some devices utilizing lipid bilayers, which include various kinds of sensors and molecular sorting devices, have been proposed. Understanding of thermal energy transfer in the lipid bilayers plays an important role in developing such devices with nano structures. In this study, we have investigated the energy transfer along and across the bilayer membrane by molecular dynamics simulations of the lipid bilayer in liquid water. We found that along the bilayer, the thermal energy is transferred by the interaction principally between water molecules and barely between lipid molecules. On the other hand, in the latter case, total thermal resistance of the lipid bilayer structure is composed of the thermal resistance of the structure’s various parts, including water, head group of lipid, and tail hydrocarbon chain of lipid, which show different values. It is found that the tail hydrocarbon chains have the highest thermal resistance.

scholarly journals Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

2020 ◽  
Vol 117 (45) ◽  
pp. 27854-27861
Author(s):  
Isabel U. Foreman-Ortiz ◽  
Dongyue Liang ◽  
Elizabeth D. Laudadio ◽  
Jorge D. Calderin ◽  
Meng Wu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Ion Channel ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Phospholipid Bilayer ◽  
Biophysical Properties ◽  
Channel Function ◽  
Dynamics Simulations ◽  
Membrane Mechanical Properties

Understanding the mechanisms of nanoparticle interaction with cell membranes is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing engineered nanomaterial safety. Much attention has focused on nanoparticles that bind strongly to biological membranes or induce membrane damage, leading to adverse impacts on cells. More subtle effects on membrane function mediated via changes in biophysical properties of the phospholipid bilayer have received little study. Here, we combine electrophysiology measurements, infrared spectroscopy, and molecular dynamics simulations to obtain insight into a mode of nanoparticle-mediated modulation of membrane protein function that was previously only hinted at in prior work. Electrophysiology measurements on gramicidin A (gA) ion channels embedded in planar suspended lipid bilayers demonstrate that anionic gold nanoparticles (AuNPs) reduce channel activity and extend channel lifetimes without disrupting membrane integrity, in a manner consistent with changes in membrane mechanical properties. Vibrational spectroscopy indicates that AuNP interaction with the bilayer does not perturb the conformation of membrane-embedded gA. Molecular dynamics simulations reinforce the experimental findings, showing that anionic AuNPs do not directly interact with embedded gA channels but perturb the local properties of lipid bilayers. Our results are most consistent with a mechanism in which anionic AuNPs disrupt ion channel function in an indirect manner by altering the mechanical properties of the surrounding bilayer. Alteration of membrane mechanical properties represents a potentially important mechanism by which nanoparticles induce biological effects, as the function of many embedded membrane proteins depends on phospholipid bilayer biophysical properties.

scholarly journals Study of Lipid Heterogeneity on Bilayer Membranes Using Molecular Dynamics Simulations

2021 ◽  
Author(s):  
G. Narahari Sastry ◽  
Nandan Kumar
Keyword(s):  
Molecular Dynamics ◽  
Human Cell ◽  
Cell Membranes ◽  
Theoretical Calculations ◽  
Structure And Function ◽  
Head Group ◽  
Membrane Thickness ◽  
Biophysical Properties ◽  
Dynamics Simulations ◽  
And Function

Abstract Human cell membranes consist of various lipids that are essential for their structure and function. Several experimental techniques have been used to characterize the composition of human cell membranes; however, it is challenging task to depict in theoretical calculations. In this work, we have investigated the structure-function relationship of lipids in both homogeneous and heterogeneous bilayer models using Molecular-Dynamics to delineate the effect of heterogeneity on the biophysical properties of membranes. Results illustrated that the biophysical properties of heterogeneous membranes are dependent on the lipid composition and concentration. We observed that the presence of cholesterol in combination with other lipids, introduced compactness of the membrane, increasing the membrane thickness. The density of lipid head group, phosphate, and glycerol-ester in presence of cholesterol with or without sphingomyelin is an underlying reason for membrane ordering. The radial distribution function shows that the cholesterol, sphingomyelin and phosphatidylethanolamine self-interaction and the interaction between cholesterol and phosphatidylethanolamine determine the structure and function of the heterogeneous membrane. Our findings provide a baseline for membrane heterogeneity that would help in understanding the physiological properties of membranes and may help to wisely select the heterogeneous bilayer model to mimic the realistic human cell membranes and the associated phenomenon.

Dynamics of Membrane-Embedded Lipid-Linked Oligosaccharides for the Three Domains of Life

2019 ◽  
Author(s):  
Pablo Ricardo Arantes ◽  
Conrado Pedebos ◽  
Laércio Pol-Fachin ◽  
Marcelo D. Poleto ◽  
Hugo Verli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Surface ◽  
Membrane Lipid ◽  
Head Group ◽  
En Bloc ◽  
Structure And Dynamics ◽  
Domains Of Life ◽  
Dynamics Simulations ◽  
Orientation Structure

<div>Lipid-linked oligosaccharides (LLOs) are the substrates of oligosaccharyltransferases (OSTs), enzymes that catalyze the en bloc transfer of a glycan chain during the process of N-glycosylation. LLOs are composed by an isoprenoid chain moiety and an oligosaccharide, linked by one or more pyrophosphate groups (PP). The lipid component on LLO is a dolichol in eukarya and archaea, and an undecaprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their metabolizing enzymes to diverse biotechnological applications, LLOs’ models from different domains of life in their native conditions could support further studies of their complexation and processing by OSTs, as well as protein engineering on such systems. Accordingly, the GROMOS53A6 force field was employed, added by GROMOS53a6GLYC parameters for the saccharidic moiety. The torsional parameters for the isoprenoid portion were derived from a fit to the proper quantum mechanical potential energy profiles at the HF 6-31G* and validated against experimental condensed phase properties. Molecular dynamics simulations employed GROMACS package to access the orientation, structure, and dynamics of eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1-GalNAc5-Bac1-PP-Undecaprenol) and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1-P-Dolichol) LLO in membrane bilayers. Microsecond molecular dynamics simulations of LLOs revealed that most carbohydrate residues interact with the membrane lipid head groups, parallel to the membrane surface, while the PP linkages are within the lipid head group, and the isoprenoid chains are within the bilayer. Overall, there are similarities in the orientations, structure, and dynamics of the eukaryotic, bacterial and archaea LLOs in bilayers. LLOs’ preferred orientation, structure and dynamics provided information for complexation with OSTs, allowing further studies of how these enzymes catalyze the transfer of the oligosaccharide chain to an acceptor protein by OSTs.</div>

scholarly journals Can we Dispense with Sphingolipids? Correlation between Membrane Lipid Composition and Biophysical Properties in Sphingolipid-Restricted Mammalian Cells

2021 ◽  
Vol 120 (3) ◽  
pp. 5a
Author(s):  
Félix M. Goñi ◽  
Bingen G. Monasterio ◽  
Noemi Jimenez-Rojo ◽  
Aritz B. Garcia-Arribas ◽  
Howard Riezman ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Mammalian Cells ◽  
Membrane Lipid ◽  
Biophysical Properties ◽  
Membrane Lipid Composition

scholarly journals A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug's biological activity

2017 ◽  
Vol 14 (133) ◽  
pp. 20170408 ◽  
Author(s):  
Ana Catarina Alves ◽  
Daniela Ribeiro ◽  
Miguel Horta ◽  
José L. F. C. Lima ◽  
Cláudia Nunes ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Lipid Bilayers ◽  
Biological Action ◽  
Model Membranes ◽  
Biophysical Properties ◽  
Biophysical Parameters ◽  
Cytotoxic Effects ◽  
Biophysical Approach ◽  
Membrane Models ◽  
Preferential Location

Daunorubicin is extensively used in chemotherapy for diverse types of cancer. Over the years, evidence has suggested that the mechanisms by which daunorubicin causes cytotoxic effects are also associated with interactions at the membrane level. The aim of the present work was to study the interplay between daunorubicin and mimetic membrane models composed of different ratios of 1,2-dimyristoyl- sn -glycero- 3 -phosphocholine (DMPC), sphingomyelin (SM) and cholesterol (Chol). Several biophysical parameters were assessed using liposomes as mimetic model membranes. Thereby, the ability of daunorubicin to partition into lipid bilayers, its apparent location within the membrane and its effect on membrane fluidity were investigated. The results showed that daunorubicin has higher affinity for lipid bilayers composed of DMPC, followed by DMPC : SM, DMPC : Chol and lastly by DMPC : SM : Chol. The addition of SM or Chol into DMPC membranes not only increases the complexity of the model membrane but also decreases its fluidity, which, in turn, reduces the amount of anticancer drug that can partition into these mimetic models. Fluorescence quenching studies suggest a broad distribution of the drug across the bilayer thickness, with a preferential location in the phospholipid tails. The gathered data support that daunorubicin permeates all types of membranes to different degrees, interacts with phospholipids through electrostatic and hydrophobic bonds and causes alterations in the biophysical properties of the bilayers, namely in membrane fluidity. In fact, a decrease in membrane fluidity can be observed in the acyl region of the phospholipids. Ultimately, such outcomes can be correlated with daunorubicin's biological action, where membrane structure and lipid composition have an important role. In fact, the results indicate that the intercalation of daunorubicin between the phospholipids can also take place in rigid domains, such as rafts that are known to be involved in different receptor processes, which are important for cellular function.

scholarly journals Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation

2017 ◽  
Vol 28 (2) ◽  
pp. 270-284 ◽  
Author(s):  
Milton To ◽  
Clark W. H. Peterson ◽  
Melissa A. Roberts ◽  
Jessica L. Counihan ◽  
Tiffany T. Wu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mammalian Cells ◽  
26S Proteasome ◽  
Unfolded Protein ◽  
Acid Analogue ◽  
Triacsin C ◽  
Chain Acyl ◽  
Dependent Cell ◽  
Outstanding Question ◽  
The Unfolded Protein Response

The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD. However, whether LDs are involved in the ERAD process remains an outstanding question. Using chemical and genetic approaches to disrupt diacylglycerol acyltransferase (DGAT)–dependent LD biogenesis, we provide evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our results suggest that triacsin C causes global alterations in the cellular lipid landscape that disrupt ER proteostasis by interfering with the glycan trimming and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the IRE1 and PERK branches of the unfolded protein response and ultimately leads to IRE1-dependent cell death. These findings identify an intimate relationship between fatty acid metabolism and ER proteostasis that influences cell viability.

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