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1.
The mechanism of the anesthetic process is of interest both to the clinician and to the pharmacologist. However, this is still an unsettled issue and a multitude of models have been proposed for the process. Noticing that most models propose either a molecular perturbation by the agents or an effect on some colligative property, we explore in this article the thermodynamical consequences of these postulations. Comparison of these with experimental findings is then made. The comparison shows the inconsistency of many of the models with the facts: (i) it refutes the long accepted conviction, culminated in the unitary hypothesis, that general anesthetics act not at a particular receptor site but invariably on all. Some consequences of this finding are demonstrated. (ii) it implies that a simple phospholipid medium is not feasible as an anesthetic site. (iii) it infers that proteins do have the properties required from anesthetic sites.Dedicated to Prof. Menachem Steinberg on the occasion of his 65th birthday 相似文献
2.
In situ pulsed force mode scanning force microscopy (PFM-SFM) images of phase separated solid-supported lipid bilayers are discussed with the help of computer simulations. Simultaneous imaging of material properties and topography in a liquid environment by means of PFM-SFM is severely hampered by hydrodynamic damping of the cantilever. Stiffness and adhesion images of solid-supported membranes consisting of cholesterol, sphingomyelin, and 1,2-dioleyl-phosphatidylcholine obtained in aqueous solution exhibit contrast inversion of adhesion and stiff. ness images depending on parameters such as driving frequency, amplitude, and trigger setting. Simulations using a simple harmonic oscillator model explain experimental findings and give a deeper insight into the way PFM-SFM experiments have to be performed in order to obtain interpretable results and hence pave the way for reliable material contrast imaging at high speed. 相似文献
3.
Corrigendum: Triazole‐Tailored Guanosine Dinucleosides as Biomimetic Ion Channels to Modulate Transmembrane Potential
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Liquid crystalline phase behaviour in model cell membranes prepared in-vitro has generated an enormous amount of interest in recent years and the phase diagrams of various bio-mimetic mixtures explored. Most recently photo-induced oxidation in fluorescently labelled membranes has been shown to influence these phase diagrams and can be used to generate interesting membrane-based geometries based on differences in membrane composition. In this article the different phases observed in model membranes will be discussed. Methods used to study these systems and recent developments in photo-stimulated phase changes are described along with areas for future investigation. 相似文献
6.
Hybrid phospholipid bilayer coatings for separations of cationic proteins in capillary zone electrophoresis
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Elyssia S. Gallagher Seid M. Adem Leonard K. Bright Isen A. C. Calderon Elisabeth Mansfield Craig A. Aspinwall 《Electrophoresis》2014,35(8):1099-1105
Protein separations in CZE suffer from nonspecific adsorption of analytes to the capillary surface. Semipermanent phospholipid bilayers have been used to minimize adsorption, but must be regenerated regularly to ensure reproducibility. We investigated the formation, characterization, and use of hybrid phospholipid bilayers (HPBs) as more stable biosurfactant capillary coatings for CZE protein separations. HPBs are formed by covalently modifying a support with a hydrophobic monolayer onto which a self‐assembled lipid monolayer is deposited. Monolayers prepared in capillaries using 3‐cyanopropyldimethylchlorosilane (CPDCS) or n‐octyldimethylchlorosilane (ODCS) yielded hydrophobic surfaces with lowered surface free energies of 6.0 ± 0.3 or 0.2 ± 0.1 mJ m?2, respectively, compared to 17 ± 1 mJ m?2 for bare silica capillaries. HPBs were formed by subsequently fusing vesicles comprised of 1,2‐dilauroyl‐sn‐glycero‐3‐phosphocholine or 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine to CPDCS‐ or ODCS‐modified capillaries. The resultant HPB coatings shielded the capillary surface and yielded reduced electroosmotic mobility (1.3–1.9 × 10?4 cm2 V?1s?1) compared to CPDCS‐ and ODCS‐modified or bare capillaries (3.6 ± 0.2 × 10?4 cm2 V?1s?1, 4.8 ± 0.4 × 10?4 cm2 V?1s?1, and 6.0 ± 0.2 × 10?4 cm2 V?1s?1, respectively), with increased stability compared to phospholipid bilayer coatings. HPB‐coated capillaries yielded reproducible protein migration times (RSD ≤ 3.6%, n ≥ 6) with separation efficiencies as high as 200 000 plates/m. 相似文献
7.
Eleni Chontzopoulou Andreas G. Tzakos Thomas Mavromoustakos 《Molecules (Basel, Switzerland)》2021,26(1)
Antagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high resolution nuclear magnetic resonance (NMR) spectroscopy in antihypertensive commercial drugs that act as AT1R antagonists. The 3D architecture of these compounds is explored through 2D NOESY spectroscopy and their interactions with micelles and lipid bilayers are described using solid state 13CP/MAS, 31P and 2H static solid state NMR spectroscopy. Due to their hydrophobic character, AT1R antagonists do not exert their optimum profile on the AT1R. Therefore, various vehicles are explored so as to effectively deliver these molecules to the site of action and to enhance their pharmaceutical efficacy. Cyclodextrins and polymers comprise successful examples of effective drug delivery vehicles, widely used for the delivery of hydrophobic drugs to the active site of the receptor. High resolution NMR spectroscopy provides valuable information on the physical-chemical forces that govern these drug:vehicle interactions, knowledge required to get a deeper understanding on the stability of the formed complexes and therefore the appropriateness and usefulness of the drug delivery system. In addition, it provides valuable information on the rational design towards the synthesis of more stable and efficient drug formulations. 相似文献
8.
Trehalose-protected lipid membranes for determining membrane protein structure and insertion 总被引:1,自引:0,他引:1
Tang M Waring AJ Hong M 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2007,184(2):222-227
Trehalose preserves lipid bilayers during dehydration and rehydration by replacing water to form hydrogen bonds between its own OH groups and lipid headgroups. We compare the lipid conformation and dynamics between trehalose-protected lyophilized membranes and hydrated membranes, to assess the suitability of the trehalose-containing membrane as a matrix for membrane protein structure determination. (31)P spectra indicate that the lipid headgroup of trehalose-protected dry POPC membrane (TRE-POPC) have an effective phase transition temperature that is approximately 50K higher than that of the hydrated POPC membrane. In contrast, the acyl chains have similar transition temperatures in the two membranes. Intramolecular lipid (13)C'-(31)P distances are the same in TRE-POPC and crystalline POPC, indicating that the lipid headgroup and glycerol backbone conformation is unaffected by trehalose incorporation. Intermolecular (13)C-(31)P distances between a membrane peptide and the lipid headgroups are 10% longer in the hydrated membrane at 226 K than in the trehalose-protected dry membrane at 253 K. This is attributed to residual motions in the hydrated membrane, manifested by the reduced (31)P chemical shift anisotropy, even at the low temperature of 226 K. Thus, trehalose lyoprotection facilitates the study of membrane protein structure by allowing experiments to be conducted at higher temperatures than possible with the hydrated membranes. 相似文献
9.
Kucerka N Pencer J Nieh MP Katsaras J 《The European physical journal. E, Soft matter》2007,23(3):247-254
The influence of cholesterol on the structure of unilamellar-vesicle (ULV) phospholipid bilayers is studied using small-angle
neutron scattering. ULVs made up of short-, mid- and long-chain monounsaturated phospholipids (diCn :1PC, n = 14 , 18, 22, respectively) are examined over a range (0-45mol %) of cholesterol concentrations. Cholesterol's effect on
bilayer structure is characterized through changes to the lipid's transmembrane thickness, lateral area and headgroup hydration.
For all three lipids, analysis of the experimental data shows that the addition of cholesterol results in a monotonic increase
of these parameters. In the case of the short- and mid-chain lipids, this is an expected result, however, such a finding was
unexpected for the long-chain lipid. This implies that cholesterol has a pronounced effect on the lipid's hydrocarbon chain
organization. 相似文献
10.