scholarly journals Discrete Conductance Fluctuations in Lipid Bilayer Protein Membranes

1969 ◽  
Vol 53 (6) ◽  
pp. 741-757 ◽  
Author(s):  
R. C. Bean ◽  
W. C. Shepherd ◽  
H. Chan ◽  
Joellen Eichner
Keyword(s):  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Membrane Lipids ◽  
Initial Reaction ◽  
Lipid Bilayer Membranes ◽  
Conductance Fluctuations ◽  
Excitable Membranes ◽  
Conductance States ◽  
High Conductance

Discrete fluctuations in conductance of lipid bilayer membranes may be observed during the initial stages of membrane interaction with EIM ("excitability inducing material"), during destruction of the EIM conductance by proteolysis, and during the potential-dependent transitions between low and high conductance states in the "excitable" membranes. The discrete conductance steps observed during the initial reaction of EIM with the lipid membranes are remarkably uniform, even in membranes of widely varying lipid composition. They range only from 2 to 6 x 10-10 ohm-1 and average 4 x 10-10 ohm-1. Steps found during destruction of the EIM conductance by proteolysis are somewhat smaller. The transition between high conductance and low conductance states may involve steps as small as 0.5 x 10-10 ohm-1. These phenomena are consistent with the formation of a stable protein bridge across the lipid membrane to provide a polar channel for the transport of cations. T6he uniform conductance fluctuations observed during the formation of these macromolecular channels may indicate that the ions in a conductive channel, in its open state, are largely protected from the influence of the polar groups of the membrane lipids. Potential-dependent changes in conductance may be due to configurational or positional changes in the protein channel. Differences in lipid-lipid and lipid-macromolecule interactions may account for the variations in switching kinetics in various membrane systems.

scholarly journals ProBLM Web Server: Protein and Membrane Placement and Orientation Package

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Taylor Kimmett ◽  
Nicholas Smith ◽  
Shawn Witham ◽  
Marharyta Petukh ◽  
Subhra Sarkar ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Lipid Bilayer ◽  
Lipid Membrane ◽  
3D Structure ◽  
Web Server ◽  
Bilayer Lipid Membrane ◽  
Lipid Bilayer Membranes ◽  
Heavy Atoms ◽  
Membrane Complex ◽  
Position And Orientation

The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of pseudoatoms. The pseudomembrane allows for modeling the desolvation effects while avoiding plausible errors associated with wrongly assigned protein-lipid contacts. The method is implemented into a web server, the ProBLM server, which is freely available to the biophysical community. The web server allows the user to upload a protein coordinate file and any missing residues or heavy atoms are regenerated. ProBLM then creates a combined protein-membrane complex from the given membrane protein and bilayer lipid membrane or pseudomembrane. The user is given an option to manually refine the model by manipulating the position and orientation of the protein with respect to the membrane.

scholarly journals Theoretical and computational modeling of peptide-lipid bilayer interaction studied by dynamic force spectroscopy

2019 ◽  
Author(s):  
◽  
Milica Utjesanovic
Keyword(s):  
Computational Modeling ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Conformational Dynamics ◽  
Quantitative Description ◽  
Md Simulations ◽  
Dynamic Force ◽  
Detachment Rate

This thesis consists of three interrelated theoretical and computational modeling projects that investigate different aspects of peptide-lipid membrane interactions. (1) A general theoretical approach is formulated for the quantitative description of the detachment force distribution, P(F), and the corresponding force dependent detachment rate, k(F), of a peptide from a lipid bilayer, by assuming that peptide detachment from lipid membranes occurs stochastically along a few dominant diffusive pathways. Besides providing a consistent interpretation of the experimental data, the new method also predicts that k(F) exhibits catch-bond behavior (when, counter intuitively, the detachment rate decreases with increasing force). (2) The proposed multiple detachment pathways method is tested and validated for a particular peptide (SecA2-11) interacting with both zwitterionic POPC lipid and polar E. Coli membranes. Furthermore, molecular dynamics (MD) simulations are used to explored the conformational dynamics of SecA2-11 during its interaction with both POPC and anionic POPG lipid bilayers. (3) Finally, MD simulations are used to explore the conformational dynamics and energetics of the peptide melittin (MWT) and its diastereomer (MD4) interacting with POPC and POPG lipid bilayers. The obtained results provide further insight into the role of secondary structure in peptide-lipid bilayer interactions.

Mechanical studies of hydrogel encapsulated membranes

2006 ◽  
Vol 926 ◽  
Author(s):  
Tae-Joon Jeon ◽  
Noah Malmstadt ◽  
Jacob Schmidt
Keyword(s):  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Mechanical Stability ◽  
Electrical Measurement ◽  
Optical Measurements ◽  
Single Channels ◽  
Lipid Bilayer Membranes ◽  
Free Standing ◽  
Intimate Contact ◽  
High Throughput Drug Screening

ABSTRACTWe have encapsulated lipid bilayer membranes within a polyethylene glycol dimethacrylate hydrogel (PEG-DMA). These hydrogel encapsulated membranes (HEMs) are significantly longer-lived and more mechanically stable than traditional lipid membranes. Over 50 attempts, HEMs usually remained intact for over 48 hours, and some lasted up to 5 days. The electrical characteristics of the HEMs were consistently stable over this period of time. The approximate thickness of the HEM was measured to be 4.7±0.5 nm (n=25), consistent with a lipid bilayer. The resistance of the HEM remained over 10 GΩ over the period of electrical measurement. Simultaneous electrical and optical measurements showed that HEMs have unusual mechanical stability, whereas free-standing lipid membranes are typically susceptible to mechanical perturbation. The HEMs could withstand much greater applied pressures than unsupported membranes. In situ electrical and optical monitoring of the HEMs showed that the gel made intimate contact with the membrane, suggesting that direct mechanical support of the bilayer is the mechanism of membrane stabilization. Single channels of alpha-hemolysin, were incorporated into HEMs and continuously measured for over 4 days. Finally, combination of the HEM with an automated membrane microfluidic formation process is proposed as a prototype platform for high throughput drug screening or small molecule sensing.

The roles of the diversity of amphipathic lipids in shaping membranes by membrane-shaping proteins

2020 ◽  
Vol 48 (3) ◽  
pp. 837-851
Author(s):  
Manabu Kitamata ◽  
Takehiko Inaba ◽  
Shiro Suetsugu
Keyword(s):  
Fatty Acid ◽  
Lipid Composition ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Membrane Lipids ◽  
Cell Types ◽  
Cellular Lipid ◽  
Head Groups ◽  
Packing Defects ◽  
Membrane Bending

Lipid compositions of cells differ according to cell types and intracellular organelles. Phospholipids are major cell membrane lipids and have hydrophilic head groups and hydrophobic fatty acid tails. The cellular lipid membrane without any protein adapts to spherical shapes, and protein binding to the membrane is thought to be required for shaping the membrane for various cellular events. Until recently, modulation of cellular lipid membranes was initially shown to be mediated by proteins recognizing lipid head groups, including the negatively charged ones of phosphatidylserine and phosphoinositides. Recent studies have shown that the abilities of membrane-deforming proteins are also regulated by the composition of fatty acid tails, which cause different degrees of packing defects. The binding of proteins to cellular lipid membranes is affected by the packing defects, presumably through modulation of their interactions with hydrophobic amino acid residues. Therefore, lipid composition can be characterized by both packing defects and charge density. The lipid composition regarding fatty acid tails affects membrane bending via the proteins with amphipathic helices, including those with the ArfGAP1 lipid packing sensor (ALPS) motif and via membrane-deforming proteins with structural folding, including those with the Bin–Amphiphysin–Rvs167 (BAR) domains. This review focuses on how the fatty acid tails, in combination with the head groups of phospholipids, affect protein-mediated membrane deformation.

scholarly journals Photosensitizing Antivirals

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3971
Author(s):  
Kseniya A. Mariewskaya ◽  
Anton P. Tyurin ◽  
Alexey A. Chistov ◽  
Vladimir A. Korshun ◽  
Vera A. Alferova ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Photophysical Properties ◽  
Short Review ◽  
Viral Envelope ◽  
Antiviral Action ◽  
Enveloped Viruses ◽  
New Compounds ◽  
Critical Consideration

Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and “phenomenological” nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (1O2). The damaging action of 1O2 on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine 1O2 photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.

scholarly journals Molecular Characterization of CNTS Mutations in Tunisian Patients with Ocular Cystinosis

2021 ◽  
Author(s):  
latifa chkioua ◽  
Yessine Amri ◽  
Chayma Saheli ◽  
Wassila Mili ◽  
Sameh Mabrouk ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Membrane Lipids ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Phospholipid Bilayer ◽  
Crystallographic Structure ◽  
Department Of Ophthalmology ◽  
Tunisian Patients

Abstract Background: Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities. Methods: This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene. Results: The studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681+7delC) and a large deletion (20327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer. Conclusion: Our data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.

scholarly journals Ophthalmic and Genetics Profiles of Cystinosis in Tunisian Patients

2021 ◽  
Author(s):  
Latifa Chkioua ◽  
Yessine Amri ◽  
Chayma Saheli ◽  
Wassila Mili ◽  
Sameh Mabrouk ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Membrane Lipids ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Phospholipid Bilayer ◽  
Crystallographic Structure ◽  
Department Of Ophthalmology ◽  
Tunisian Patients

Abstract Background: Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities. Methods: This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene. Results: The studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681+7delC) and a large deletion (20327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer. Conclusion: Our data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.

scholarly journals Electrochemical Properties of Lipid Membranes Self-Assembled from Bicelles

Membranes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Damian Dziubak ◽  
Kamil Strzelak ◽  
Slawomir Sek
Keyword(s):  
Electrochemical Properties ◽  
Self Assembly ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Membrane Resistance ◽  
Electrochemical Characteristics ◽  
Freeze Thaw ◽  
Lipid Films ◽  
Supported Lipid Membranes

Supported lipid membranes are widely used platforms which serve as simplified models of cell membranes. Among numerous methods used for preparation of planar lipid films, self-assembly of bicelles appears to be promising strategy. Therefore, in this paper we have examined the mechanism of formation and the electrochemical properties of lipid films deposited onto thioglucose-modified gold electrodes from bicellar mixtures. It was found that adsorption of the bicelles occurs by replacement of interfacial water and it leads to formation of a double bilayer structure on the electrode surface. The resulting lipid assembly contains numerous defects and pinholes which affect the permeability of the membrane for ions and water. Significant improvement in morphology and electrochemical characteristics is achieved upon freeze–thaw treatment of the deposited membrane. The lipid assembly is rearranged to single bilayer configuration with locally occurring patches of the second bilayer, and the number of pinholes is substantially decreased. Electrochemical characterization of the lipid membrane after freeze–thaw treatment demonstrated that its permeability for ions and water is significantly reduced, which was manifested by the relatively high value of the membrane resistance.

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