scholarly journals Effect of Peptide PV on the Ionic Permeability of Lipid Bilayer Membranes

1974 ◽  
Vol 63 (4) ◽  
pp. 492-508 ◽  
Author(s):  
H. P. Ting-Beall ◽  
M. T. Tosteson ◽  
B. F. Gisin ◽  
D. C. Tosteson

This paper reports the effects of peptide PV (primary structure: cyclo-(D-val-L-pro-L-val-D-pro)δ) on the electrical properties of sheep red cell lipid bilayers. The membrane conductance (Gm) induced by PV in either Na+ or K+ medium is proportional to the concentration of PV in the aqueous phase. The PV concentration required to produce a comparable increase in Gm in K+ medium is about 104 times greater than for its analogue, valinomycin (val). Although the selectivity sequence for PV and val is similar, K+ ≳ Rb+ > Cs+ > NH4+ > TI+ > Na+ > Li+; the ratio of GGm in K+ to that in Na+ is about 10 for PV compared to > 103 for val. When equal concentrations of PV are added to both sides of a bilayer, the membrane current approaches a maximum value independent of voltage when the membrane potential exceeds 100 mV. When PV is added to only one side of a bilayer separating identical salt solutions of either Na+ or K+ salts, rectification occurs such that the positive current flows more easily away rather than toward the side containing the carrier. Under these conditions, a large, stable, zero-current potential (VVm) is also observed, with the side containing PV being negative. The magnitude of this VVm is about 90 mV and relatively independent of PV concentration when the latter is larger than 2 Times; 10–5 M. From a model which assumes that Vm equals the equilibrium potential for the PV-cation complexes (MS+) and that the reaction between PV and cations is at equilibrium on the two membrane surfaces, we compute the permeability of the membrane to free PV to be about 10–5 cm s–1, which is about 10–7 times the permeability of similar membranes to free val. This interpretation is supported by the fact that the observed values of Vm are in agreement with the calculated equilibrium potential for MS+ over a wide range of ratios of concentrations of total PV in the two bathing solutions, if the unstirred layers are taken into account in computing the MS+ concentrations at the membrane surfaces.

1978 ◽  
Vol 71 (3) ◽  
pp. 269-284 ◽  
Author(s):  
J Gutknecht ◽  
J S Graves ◽  
D C Tosteson

The permeability properties of planar lipid bilayers made from egg lecithin, n-decane and a long-chain secondary amine (n-lauryl [trialkylmethyl]amine) are described. Membranes containing the secondary amine show halide selectivity and high conductance at pH less than 6, as estimated by measurements of zero-current potentials generated by NaBr activity gradients. In the absence of halide ions, the membranes show H+ selectivity, although the total membrane conductance is relatively low. In 0.1 M NaBr both the membrane conductance (Gm) and the Br- self-exchange flux (JBr) are proportional to H+ concentration over the pH range of 7 to 4, and both JBr and Gm saturate at pH less than 4. However, JBr is always more than 100 times the flux predicted from Gm and the transference number for Br-. Thus, greater than 99% of the observed (tracer) flux is electrically silent and is not a Br2 or HBrO flux because the reducing agent, S2O3=, has no effect on JBr. At pH 7, JBr is proportional to Br- concentration over the range of 1-340 mM, with no sign of saturation kinetics. Both urea and sulfate tracer permeabilities are low and are unaffected by pH. The results can be explained by a model in which the secondary amine behaves as a monovalent, titratable carrier which exists in three chemical forms (C, CH+, and CHBr). Br- crosses the membrane primarily as the neurtal complex (CHBr). The positively charged carrier (CH+) crosses the membrane slowly compared to CHBr, but CH+ is the principal charge carrier in the membrane. At neurtal pH greater than 99% of the amine is in the nonfunctional form (C), which can be converted to CH+ or CHBr by increasing the H+ or Br- concentrations. The permeability properties of these lipid bilayers resemble in many respects the permeability properties of red cell membranes.


2016 ◽  
Vol 147 (4) ◽  
pp. 291-308 ◽  
Author(s):  
Thomas Holm Pedersen ◽  
Anders Riisager ◽  
Frank Vincenzo de Paoli ◽  
Tsung-Yu Chen ◽  
Ole Bækgaard Nielsen

Electrical membrane properties of skeletal muscle fibers have been thoroughly studied over the last five to six decades. This has shown that muscle fibers from a wide range of species, including fish, amphibians, reptiles, birds, and mammals, are all characterized by high resting membrane permeability for Cl− ions. Thus, in resting human muscle, ClC-1 Cl− ion channels account for ∼80% of the membrane conductance, and because active Cl− transport is limited in muscle fibers, the equilibrium potential for Cl− lies close to the resting membrane potential. These conditions—high membrane conductance and passive distribution—enable ClC-1 to conduct membrane current that inhibits muscle excitability. This depressing effect of ClC-1 current on muscle excitability has mostly been associated with skeletal muscle hyperexcitability in myotonia congenita, which arises from loss-of-function mutations in the CLCN1 gene. However, given that ClC-1 must be drastically inhibited (∼80%) before myotonia develops, more recent studies have explored whether acute and more subtle ClC-1 regulation contributes to controlling the excitability of working muscle. Methods were developed to measure ClC-1 function with subsecond temporal resolution in action potential firing muscle fibers. These and other techniques have revealed that ClC-1 function is controlled by multiple cellular signals during muscle activity. Thus, onset of muscle activity triggers ClC-1 inhibition via protein kinase C, intracellular acidosis, and lactate ions. This inhibition is important for preserving excitability of working muscle in the face of activity-induced elevation of extracellular K+ and accumulating inactivation of voltage-gated sodium channels. Furthermore, during prolonged activity, a marked ClC-1 activation can develop that compromises muscle excitability. Data from ClC-1 expression systems suggest that this ClC-1 activation may arise from loss of regulation by adenosine nucleotides and/or oxidation. The present review summarizes the current knowledge of the physiological factors that control ClC-1 function in active muscle.


Author(s):  
David W. Deamer

In the absence of self-assembly processes, life as we know it would be impossible. This chapter begins by introducing self-assembly then focuses on the primary functions of membranes in living cells, most of which depend on highly evolved proteins embedded in lipid bilayers. These serve to capture light energy in photosynthesis and produce ion concentration gradients from which osmotic energy can be transduced into chemical energy. Although lipid bilayer membranes provide a permeability barrier, they cannot be absolutely impermeable because intracellular metabolic functions depend on external sources of nutrients. Therefore, another set of embedded proteins evolved to form transmembrane channels that allow selective permeation of certain solutes. The earliest life did not have proteins available, so in their absence what was the primary function of membranous compartments in prebiotic conditions? There are three possibilities. First, the compartments would allow encapsulated polymers to remain together as random mixtures called protocells. Second, populations of protocells that vary in composition would be subject to selective processes and the first steps of evolution. Even though any given protocell would be only transiently stable, certain mixtures of polymers would tend to stabilize the surrounding membrane. Such an encapsulated mixture would persist longer than the majority that would be dispersed and recycled, and these more robust protocells would tend to emerge as a kind of species. Last and perhaps most important, there had to be a point in early evolution at which light energy began to be captured by membranous structures, just as it is today. Bilayer membranes are not necessarily composed solely of amphiphilic molecules. They can also contain other nonpolar compounds that happen to be pigments capable of capturing light energy. This possibility is almost entirely unexplored, but the experiments are obvious and would be a fruitful focus for future research. Questions to be addressed: What is meant by self-assembly? Why is self-assembly important for the origin of life? What compounds can undergo self-assembly processes? How can mixtures of monomers and lipids assemble into protocells? We tend to think of living cells in terms of directed assembly.


2000 ◽  
Vol 182 (18) ◽  
pp. 5251-5255 ◽  
Author(s):  
Fiona S. L. Brinkman ◽  
Manjeet Bains ◽  
Robert E. W. Hancock

ABSTRACT Pseudomonas aeruginosa OprF forms 0.36-nS channels and, rarely, 2- to 5-nS channels in lipid bilayer membranes. We show that a protein comprising only the N-terminal 162-amino-acid domain of OprF formed the smaller, but not the larger, channels in lipid bilayers. Circular dichroism spectroscopy indicated that this protein folds into a β-sheet-rich structure, and three-dimensional comparative modeling revealed that it shares significant structural similarity with the amino terminus of the orthologous protein Escherichia coliOmpA, which has been shown to form a β-barrel. OprF and OmpA share only 15% identity in this domain, yet these results support the utility of modeling such widely divergent β-barrel domains in three dimensions in order to reveal similarities not readily apparent through primary sequence comparisons. The model is used to further hypothesize why porin activity differs for the N-terminal domains of OprF and OmpA.


2011 ◽  
Vol 21 (05) ◽  
pp. 1027-1042 ◽  
Author(s):  
MICHAEL HELMERS

In order to study a one-dimensional analogue of the spontaneous curvature model for two-component lipid bilayer membranes, we consider planar curves that are made of a material with two phases. Each phase induces a preferred curvature to the curve, and these curvatures as well as phase boundaries may lead to the development of kinks. We introduce a family of energies for smooth curves and phase fields, and we show that these energies Γ-converge to an energy for curves with a finite number of kinks. The theoretical result is illustrated by some numerical examples.


1972 ◽  
Vol 60 (1) ◽  
pp. 72-85 ◽  
Author(s):  
Ramon Latorre ◽  
Gerald Ehrenstein ◽  
Harold Lecar

Two different methods were used to determine the relative permeability and the voltage-dependent conductance of several different cations in excitability-inducing material (EIM)-doped lipid bilayers. In one method, the conductances of individual channels were measured for Li, Na, K, Cs, NH4, and Ca, and in the other method biionic potentials of a membrane with many channels were measured for Li, Na, K, Cs, and Rb. The experimental results for the two methods are in agreement. The relative permeabilities are proportional to the ionic mobilities in free aqueous solution. The voltage dependence of the conductance is the same for all cations measured.


1998 ◽  
Vol 76 (2-3) ◽  
pp. 452-464 ◽  
Author(s):  
Peter M Macdonald ◽  
Kevin J Crowell ◽  
Carla M Franzin ◽  
Peter Mitrakos ◽  
Darlene J Semchyschyn

Domain formation in lipid bilayer membranes can occur through electrostatic interactions between charged lipids and oppositely charged polyelectrolytes, such as proteins or polynucleic acids. This review describes a novel method for examining such domains in lipid bilayers, based on 2H NMR spectroscopy. The 2H NMR spectrum of choline-deuterated phosphatidylcholine is sensitive to, and reports on, lipid bilayer surface charge. When a charged lipid bilayer is exposed to an oppositely charged polyelectrolyte, the latter binds electrostatically to the bilayer surface and attracts charged lipids into its vicinity. The resulting inhomogeneous charge distribution produces overlapping 2H NMR subspectra arising from phosphatidylcholine within charge-enriched versus charge-depleted regions. Such spectral details as the quadrupolar splittings and the relative intensities of the subspectra permit a complete analysis of the domain composition, size, and, within limits, lifetime. Using 2H NMR, domain formation in lipid bilayer membranes can be observed with both cationic and anionic polyelectrolytes, whether of natural or synthetic origin. Domain size and composition prove to be sensitive to the detailed chemical structure of both the polyelectrolyte and the charged lipids. Within the domains there is always a stoichiometric anion/cation binding ratio, indicating that the polyelectrolyte lies flat on the membrane surface. The amount of phosphatidylcholine within the domain varies as a function of its statistical availability, in accordance with the predictions of a recent thermodynamic model of domain formation. When the molecular weight of the polyelectrolyte is varied, the domain size alters in accordance with the predictions of classical polymer physics. As expected for a predominantly electrostatic phenomenon, the observed domains dissipate at high ionic strength.Key words: electrostatic domains, polyelectrolytes, lipid bilayers, deuterium NMR.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Vamshi K. Gangupomu ◽  
Franco M. Capaldi

Understanding the interaction between a carbon nanotube and biological macromolecules such as lipid bilayers is important for the design and development of nanovectors for gene and drug delivery. The forces of penetration and the free energies of rupture of lipid bilayers during nanotube penetration were studied using nonequilibrium, all-atom molecular dynamics simulations for pure POPC and POPC/cholesterol bilayers. The presence of cholesterol did not alter the magnitude of the rupture force and minimally increased the estimated free energy of rupture. However, the ability of the nanotube to disrupt the membrane leading to membrane poration increased with increasing cholesterol content.


2021 ◽  
Vol 22 (19) ◽  
pp. 10553
Author(s):  
Ari Ogaki ◽  
Yuji Ikegaya ◽  
Ryuta Koyama

Extracellular vesicles (EVs) are composed of lipid bilayer membranes and contain various molecules, such as mRNA and microRNA (miRNA), that regulate the functions of the recipient cell. Recent studies have reported the importance of EV-mediated intercellular communication in the brain. The brain contains several types of cells, including neurons and glial cells. Among them, astrocytes are the most abundant glial cells in the mammalian brain and play a wide range of roles, from structural maintenance of the brain to regulation of neurotransmission. Furthermore, since astrocytes can take up EVs, it is possible that EVs originating from inside and outside the brain affect astrocyte function, which in turn affects brain function. However, it has not been fully clarified whether the specific targeting mechanism of EVs to astrocytes as recipient cells exists. In recent years, EVs have attracted attention as a cell-targeted therapeutic approach in various organs, and elucidation of the targeting mechanism of EVs to astrocytes may pave the way for new therapies for brain diseases. In this review, we focus on EVs in the brain that affect astrocyte function and discuss the targeting mechanism of EVs to astrocytes.


2002 ◽  
Vol 18 (4) ◽  
pp. 185-191 ◽  
Author(s):  
John J. Kasianowicz

Several classes of transmembrane protein ion channels function in vivo as sensitive and selective detection elements for analytes. Recent studies on single channels reconstituted into planar lipid bilayer membranes suggest that nanometer-scale pores can be used to detect, quantitate and characterize a wide range of analytes that includes small ions and single stranded DNA. We briefly review here these studies and identify leaps in technology that, if realized, might lead to innovations for the early detection of cancer.


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