Lipid diffusion, free area, and molecular dynamics simulations.
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Animals↗
Biomedical subjects
T E Thompson
Publications and source records attributed to T E Thompson.
Partitioning of amphiphiles between coexisting ordered and disordered phases in two-phase lipid bilayer membranes.
The partition coefficients (K(P)) of a series of single-chain and double-chain fluorescent amphiphiles, between solid ordered (P(beta') and L(beta)) and liquid disordered (L(alpha) of the type l(d)) lipid phases coexisting in the same lipid bilayer, was studied using steady-state fluorescence emission anisotropy. The single-chain amphiphiles were N-(7-nitrobenzoxa-2, 3-diazol-4-yl)-alkylamines, and the double-chain amphiphiles were N-(7-nitrobenzoxa-2, 3-diazol-4-yl)-phosphatidylethanolamines with chain lengths of 12-18 carbon atoms. Saturated 18-carbon alkyl/acyl chain compounds were also compared with Delta(9)-cis unsaturated chains of the same chain length. The fluorescence anisotropy of the probes was examined in lipid bilayers (multilamellar vesicles) prepared from an equimolar mixture of dilauroylphosphatidylcholine and distearoylphosphatidylcholine and studied as a function of temperature through the entire temperature range of coexistence of ordered gel phases and a disordered fluid phase in this system. The unsaturated chain amphiphiles partitioned exclusively into the fluid phase whenever this phase was present, as did the saturated chain amphiphiles with the shortest chains (C(12:0)), while K(P) ranges between 1 and 2, in favor of the L(beta) solid phase, for the amphiphiles with long saturated (C(18:0)) alkyl/acyl chains, with intermediate behavior for the intermediate chain lengths. All probes appeared to be totally excluded from P(beta') solid (gel) phases. The technique was also used to determine partitioning of some of the probes between coexisting liquid ordered (cholesterol-containing) (l(o)) and liquid disordered (l(d)) L(alpha) phases. In this case the ratio of signal amplitude to noise allowed us to obtain a qualitative, but not quantitative, measure of the phase partitioning of the probes. We conclude that the partitioning behavior of the probes examined between coexisting l(o) and l(d) phases is qualitatively similar to that observed between solid ordered and liquid disordered phases.
Fluorescence Polarization↗
Monte Carlo simulation of two-component bilayers: DMPC/DSPC mixtures.
In this paper, we describe a relatively simple lattice model of a two-component, two-state phospholipid bilayer. Application of Monte Carlo methods to this model permits simulation of the observed excess heat capacity versus temperature curves of dimyristoylphosphatidylcholine (DMPC)/distearoylphosphatidylcholine (DSPC) mixtures as well as the lateral distributions of the components and properties related to these distributions. The analysis of the bilayer energy distribution functions reveals that the gel-fluid transition is a continuous transition for DMPC, DSPC, and all DMPC/DSPC mixtures. A comparison of the thermodynamic properties of DMPC/DSPC mixtures with the configurational properties shows that the temperatures characteristics of the configurational properties correlate well with the maxima in the excess heat capacity curves rather than with the onset and completion temperatures of the gel-fluid transition. In the gel-fluid coexistence region, we also found excellent agreement between the threshold temperatures at different system compositions detected in fluorescence recovery after photobleaching experiments and the temperatures at which the percolation probability of the gel clusters is 0.36. At every composition, the calculated mole fraction of gel state molecules at the fluorescence recovery after photobleaching threshold is 0.34 and, at the percolation threshold of gel clusters, it is 0.24. The percolation threshold mole fraction of gel or fluid lipid depends on the packing geometry of the molecules and the interchain interactions. However, it is independent of temperature, system composition, and state of the percolating cluster.
Dimyristoylphosphatidylcholine↗
Sphingomyelin: biophysical aspects.
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Animals↗
Chain length and temperature dependence of the reversible association of model acylated proteins with lipid bilayers.
To study the binding of fatty-acylated proteins to lipid bilayers, we have specifically attached fatty acids to the N-terminus of chemically modified bovine pancreatic trypsin inhibitor. This was accomplished by reacting the protein with saturated fatty acid anhydrides ranging in length from 8 to 18 carbons. Following radiolabeling of the fatty-acylated proteins at Lys-15, binding of these proteins to palmitoyloleoyl phosphatidylcholine vesicles was examined as a function of temperature using ultracentrifugation to determine the fraction of bound protein. Binding of these fatty-acylated proteins exhibited a significant enthalpy change. We also examined the free-energy change of binding as a function of fatty acid chain length. Our results are complimentary to other binding studies of fatty-acylated peptides. Comparisons with other myristoylated proteins and peptides indicate that local protein structure, apart from electrostatic interactions, plays a significant role in determining the magnitude of the overall free-energy change of membrane binding of fatty-acylated proteins. Light-scattering experiments indicated that both myristoyl and palmitoyl groups can induce protein micelle formation in aqueous solution at high concentration, but that only palmitoyl groups do so at physiologically relevant concentrations. Our results support a model in which single lipid modifications are incapable of stably anchoring proteins to biological membranes but facilitate protein associations in conjunction with other modes of interaction.
Acylation↗
Estrogen upregulation of BRCA1 expression with no effect on localization.
Alterations in the expression of the breast and ovarian cancer susceptibility gene BRCA1 may contribute to the development of mammary and ovarian neoplasia. The sex-steroid estrogen modulates cell proliferation of normal and neoplastic breast and ovarian epithelial cells, but the role of estrogen regulation on the expression of BRCA1 remains to be defined. In this study, estrogen-regulated BRCA1 expression was examined in breast and ovarian cancer cells. Estrogen stimulated the proliferation of estrogen receptor (ER)-positive breast MCF-7, C7-MCF-7, and ovarian BG-1 cells as well as the expression of the estrogen-inducible pS2 gene. This was concomitant with upregulation of BRCA1 mRNA (2.5- to 5.0-fold) and a 3- to 10-fold induction of BRCA1 protein (230 kDa). Cell fractionation studies localized the BRCA1 protein to the nucleus in both unstimulated and estrogen-stimulated cells. The antiestrogen ICI-182780 inhibited estrogen-induced cell proliferation, BRCA1 mRNA induction, and BRCA1 protein expression in ER-positive cells. Conversely, estrogen did not influence expression of BRCA1 in HBL-100 cells that lacked the estrogen receptor, although the constitutive levels of BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in other breast and ovarian cancer cells. Secretion of the BRCA1 protein into the cell medium did not account for the discrepancy between the mRNA and protein levels in HBL-100 cells. Proliferation of HBL-100 cells was not affected by either estrogen or ICI-182780. Taken together, these data support a role for the steroid estrogen and the involvement of the estrogen receptor pathway in the modulation of expression of BRCA1. We therefore propose that stimulation of cell proliferation may be a prerequisite for upregulation of BRCA1 in breast and ovarian cancer cells.
Antineoplastic Agents↗
Effect of sphingomyelin composition on the phase structure of phosphatidylcholine-sphingomyelin bilayers.
In this study, we examine the phase behavior as well as lateral diffusion and percolation in the region of coexisting gel and fluid phases in binary mixtures composed of dimyristoylphosphatidylcholine and one of two totally synthetic D-erythro-sphingomyelins (having either C16 or C24 acyl chains, both having similar gel to liquid-crystalline phase transition temperatures). This study stems from the uniqueness of sphingomyelins having gel to liquid-crystalline transition temperatures in the range of physiological interest, and the fact that more than 50% of the naturally occurring sphingomyelin species have a chain mismatch. The presence of sphingomyelin in biological membranes can thus be expected to give rise to a complex phase structure. Fluorescence recovery after photobleaching, differential scanning calorimetry, and electron microscopy are used to show that, despite similarity in the temperature range of the gel to liquid-cystalline phase transition of the two sphingomyelins, the two differ in their phase structure. Also they differ to a large extent in their mixing with dimyristoylphosphatidylcholine. Dimyristoylphosphatidylcholine and C16 sphingomyelin mix nearly ideally, with the percolation threshold locus lying close to the liquidus on the phase diagram. In contrast, the C24 sphingomyelin and dimyristoylphosphatidylcholine mix nonideally, with the percolation threshold locus lying close to the solidus. In addition, mixtures containing C24 sphingomyelin have a complex thermotropic behavior which may be related to the observation that these dispersions contain several types of particles, some of which are not multilamellar vesicles. These studies suggest that the degree of sphingomyelin chain mismatch is an important factor in determining lateral organization in the membrane.
Calorimetry, Differential Scanning↗
Influence of the intrinsic membrane protein bacteriorhodopsin on gel-phase domain topology in two-component phase-separated bilayers.
We have investigated the effect of the intrinsic membrane protein bacteriorhodopsin of Halobacterium halobium on the lateral organization of the lipid phase structure in the coexistence region of an equimolar mixture of dimyristoylphos-phatidylcholine and distearoylphosphatidylcholine. The fluorescence recovery after photobleaching (FRAP) technique was used to monitor the diffusion of both a lipid analog (N-(7-nitrobenzoxa-2,3-diazol-4-yl)-dimyristoylphosphatidyle thanolamine, NBD-DMPE) and fluorescein-labeled bacteriorhodopsin (Fl-BR). In the presence of bacteriorhodopsin, the mobile fractions of the two fluorescent probes display a shift of the percolation threshold toward lower temperatures (larger gel-phase fractions), independent of the protein concentration, from 43 degrees C (without bacteriorhodopsin) to 39 degrees C and 41 degrees C for NBD-DMPE and Fl-BR, respectively. Moreover, in the presence of bacteriorhodopsin, the gel-phase domains are much less efficient in restricting the diffusion of both probes than they are in the absence of the protein in the two-phase coexistence region. Bacteriorhodopsin itself, however, obstructs diffusion of NBD-DMPE and Fl-BR to about the same extent in the fluid phase of the two-phase region as it does in the homogeneous fluid phase. These observations suggest that 1) the protein induces the formation of much larger and/or more centrosymmetrical gel-phase domains than those formed in its absence, and 2) bacteriorhodopsin partitions almost equally between the coexisting fluid and gel phases. Although the molecular mechanisms involved are not clear, this phenomenon is fully consistent with the effect of the transmembrane peptide pOmpA of Escherichia coli investigated by electron spin resonance in the same lipid system.
Affinity Labels↗
Fluorescence quenching and electron spin resonance study of percolation in a two-phase lipid bilayer containing bacteriorhodopsin.
The effect of bacteriorhodopsin (BR) on the percolation properties of dimyristoylphosphatidylcholine/distearoylphosphatidylcholine bilayers was examined by studying the quenching of a lipid-bound fluorophore by a lipid-bound quencher, and by spin-spin interactions of a nitroxide-labeled lipid using electron spin resonance (ESR). At the low concentrations of BR used, differential scanning calorimetry showed that although the transition enthalpy was reduced in a concentration-dependent manner by incorporation of BR, the solidus and fluidus phase boundaries and overall shape of the heat capacity profiles were essentially unchanged. However, fluorescence quenching and spin-label ESR data showed that the domain topology, as reflected in the percolation properties, is strongly affected by the protein. In contrast to our previous fluorescence data for the pure lipid mixtures, quenching in the coexistence region is independent of the fluid phase fraction when BR is present. In addition, the percolation threshold estimated by spin-label ESR is shifted in the presence of BR to a higher gel phase fraction at a given lipid composition. Both the fluorescence quenching and spin-label ESR data, together with the results of earlier simulations, strongly suggest that the fluid phase domains are substantially larger and/or less ramified in the presence of BR than in its absence. We have previously reported a similar effect of a transmembrane peptide, pOmpA (Escherichia coli outer membrane protein A signal peptide), on fluid domain connectivity in binary phosphatidylcholine mixtures.
Bacteriorhodopsins↗
Design of membrane-inserting peptides: spectroscopic characterization with and without lipid bilayers.
This paper reports the spectroscopic characterization of two de novo peptides. The first sequence, Ala peptide = H2N-Ala27-Tyr-Lys6-CONH2, gives circular dichroism (CD) and Fourier transform infrared (FTIR) spectra characteristic of beta structure in solution, binds to lipid bilayer vesicles poorly, and tends to precipitate in buffered 0.1 M salt solutions. In the second sequence, Leu peptide = H2N-Ala2-Leu3-Ala22-Tyr-Lys6-CONH2, three leucines are substituted for three alanine residues. This small sequence change results in CD spectra that are characteristic of helical structures, while the FTIR spectra give evidence for complex equilibria between multiple structures in solution. The Leu peptide does not precipitate in buffered salt solutions and binds to lipid bilayers. The polarized attenuated total reflectance infrared spectra provide evidence of a transmembrane orientation for the helical peptide in lipid bilayers. The collective spectroscopic results are summarized in a tentative model in which the Leu peptide exhibits multiple equilibria between extended unordered, helix, and coiled-coil structures in solution; when lipid vesicles are added, the peptide binds to the lipid surface and then inserts into the lipid in a transmembrane orientation. The slow kinetics exhibited by the peptide suggest multiple conformational changes during the lipid-peptide interactions. The design rationale for the peptides is included in an appendix.
Amino Acid Sequence↗
Fluorescence-quenching study of percolation and compartmentalization in two-phase lipid bilayers.
Fluorescence quenching of a lipid-labeled fluorophore by a lipid spin-labeled quencher has been studied experimentally in two-component, two-phase phosphatidylcholine bilayers to examine the effect of phase connection and disconnection on quenching. Both fluorophore and quencher prefer the fluid phase. At the percolation threshold, the point at which the fluid phase becomes subdivided into may small disconnected domains, the quenching drops abruptly. This decrease in quenching is a function of the fluid-phase fraction and is due to the heterogeneous distribution of fluorophores and quenchers over the fluid-phase domains. Computer simulations of the system were carried out with a triangular lattice divided into closed compartments of variable size and reactant occupancy. The simulations demonstrate that the degree of quenching is reduced in the disconnected systems and that the reduction is correlated with the size of the disconnected domains. The combination of experimental data with simulations leads to the conclusion that at constant temperature the size of fluid-phase domains, nfluid, in the region of the coexistence of the fluid and gel phases is proportional to the fluid fraction, Xfluid. This is in a qualitative agreement with a previous electron spin resonance study of interlipid spin-spin interactions in the same two-component, two-phase bilayer system.
1,2-Dipalmitoylphosphatidylcholine↗
Topology of gel-phase domains and lipid mixing properties in phase-separated two-component phosphatidylcholine bilayers.
The influence of the lipid mixing properties on the lateral organization in a two-component, two-phase phosphatidylcholine bilayer was investigated using both an experimental (fluorescence recovery after photobleaching (FRAP)) and a simulated (Monte Carlo) approach. With the FRAP technique, we have examined binary mixtures of 1-stearoyl-2-capryl-phosphatidylcholine/1,2-distearoyl-phosphat idylcholine (C18C10PC/DSPC), and 1-stearoyl-2-capryl-phosphatidylcholine/1,2-dipalmitoyl-phospha tid ylcholine (C18C10PC/DPPC). Comparison with the 1,2-dimyristoyl-phosphatidylcholine/1,2-distearoyl-phosphatidylcholine (DMPC/DSPC) previously investigated by FRAP by Vaz and co-workers (Biophys. J., 1989, 56:869-876) shows that the gel phase domains become more effective in restricting the diffusion coefficient when the ideality of the mixture increases (i.e., in the order C18C10PC/DSPC-->C18C10PC/DPPC-->DMPC/DSPC). However, an increased lipid miscibility is accompanied by an increasing compositional dependence: the higher the proportion of the high-temperature melting component, the less efficient the gel phase is in compartmentalizing the diffusion plane, a trend that is best accounted for by a variation of the gel phase domain shape rather than size. Computer-simulated fluorescence recoveries obtained in a matrix obstructed with obstacle aggregates of various fractal dimension demonstrate that: 1) for a given obstacle size and area fraction, the relative diffusion coefficient increases linearly with the obstacle fractal dimension and 2) aggregates with a lower fractal dimension are more efficient in compartmentalizing the diffusion plane. Comparison of the simulated with the experimental mobile fractions strongly suggests that the fractal dimension of the gel phase domains increases with the proportion of high-temperature melting component in DMPC/DSPC and (slightly) in C18C10PC/DPPC.
1,2-Dipalmitoylphosphatidylcholine↗
Gel phase preference of ganglioside GM1 at low concentration in two-component, two-phase phosphatidylcholine bilayers depends upon the ceramide moiety.
In two-component phosphatidylcholine bilayers with coexisting liquid and P beta' gel phases, the distribution between phases of low concentrations of glycosphingolipids can be determined by freeze-etch electron microscopy after labeling the glycolipid with a suitable protein. We have found that the distribution depends upon the glycosphingolipid species (Rock, P. et al., (1991) Biochemistry 30, 19-25). Using this technique with cholera toxin as the protein label and bilayers formed from dipalmitoyl- and dielaidoylphosphatidylcholine (1:1) containing < 1 mol% GM1, we have studied the distribution of a family of GM1 homologues differing in the acyl chain and sphingoid base moieties. The GM1 preference for the P beta' ripple phase decreases with decreasing acyl chain length and increasing unsaturation. GM1 with either a C18:1 or C20:1 sphingoid base shows similar distributions in liquid and gel phases. When the molecules are preferentially found in the P beta' phase, they are positioned along unique loci in both A and A/2 forms of the ripple structure. This localization and acyl chain dependence reflect the volume, shape and localization of molecular packing defects in the P beta' phase. The ganglioside inclusions stabilize the P beta' phase and form compositional domains of unique topography.
Animals↗
Interdigitation does not affect translational diffusion of lipids in liquid crystalline bilayers.
Asymmetric phosphatidylcholine molecules with one acyl chain twice as long as the other, below their phase transition temperature, from a mixed interdigitated phase in which the longer acyl chain spans the entire bilayer. Experimental evidence in the literature suggests that, above their phase transition temperature, these molecules may still exhibit partial interdigitation, with the longer acyl chain extending partially into the opposite leaflet, and are packed more tightly than equivalent symmetric phosphatidylcholines. Using the fluorescence recovery after photobleaching technique, we have investigated the translational diffusion in multilayers of a liquid crystalline phase, asymmetric phosphatidylcholine, 1-stearoyl-2-capryl-phosphatidylcholine (C18C10PC). We used as a fluorescent probe either a phospholipid analog of the same acyl chain composition, NBD-C18C10PE, or the symmetric equivalent of the same molecular weight, N-(7-nitrobenzoxa-2,3-diazol-4-yl)-dimyristoyl-phosphatidyle thanolamine (NBD-DMPE). Translational diffusion coefficients were also determined by using both probes in multilayers of dimyristoyl-phosphatidylcholine (DMPC) and in the eutectic mixture DMPC/C18C10PC (40/60 mol). We found that in a given host lipid, NBD-C18C10PE and NBD-DMPE diffuse at the same rate, which suggests that their bilayer free area is almost identical. This result can be explained by considering that in the liquid crystalline state, the increase in molecular packing is compensated by an increase in acyl chain dynamics. This view, which is supported by literature data, clearly suggests that the acyl chain interdigitation occurring in the liquid crystalline phase is highly dynamic.
4-Chloro-7-nitrobenzofurazan↗
Permeability of dimyristoyl phosphatidylcholine/dipalmitoyl phosphatidylcholine bilayer membranes with coexisting gel and liquid-crystalline phases.
The passive permeation of glucose and a small zwitterionic molecule, methyl-phosphoethanolamine, across two-component phospholipid bilayers (dimyristoyl phosphatidylcholine (DMPC)/dipalmitoyl phosphatidylcholine (DPPC) mixtures) exhibit a maximum when gel domains and fluid domains coexist. The permeability data of the two-phase bilayers cannot be fitted to single-rate kinetics, but are consistent with a Gaussian distribution of rate constants. In pure DMPC and DPPC as well as in their mixtures, at the temperature of the maximum excess heat capacity, the logarithm of the average permeability rate constants are linearly correlated with the mole fraction of DPPC in the total system. In addition, in the 50:50 mixture, the excess heat capacity values as well as the apparent fractions of interfacial lipid correlate with the logarithm of the excess permeabilities in the two-phase region. These results suggest that small polar molecules can cross the membrane at the interface between gel and fluid domains at a much faster rate than through the homogeneous phases; the acyl chains located at the domain interface experience lateral density fluctuations that are inversely proportional to their average length, and large enough to allow rapid transmembrane diffusion of the solute molecules. The distribution of the permeability rate constants may reflect temporal and spatial fluctuations of the lipid composition at the phase boundaries.
1,2-Dipalmitoylphosphatidylcholine↗
Semisynthetic proteins: model systems for the study of the insertion of hydrophobic peptides into preformed lipid bilayers.
Models of protein translocation and secretion will not be complete without details of the mechanism of lipid bilayer insertion. The study of spontaneous hydrophobic peptide interactions with model membrane systems has been hindered by their very low solubility in aqueous solutions. A novel protocol has been developed that enables the site-specific (N-terminus) attachment of hydrophobic peptides to a water-soluble carrier protein [bovine pancreatic trypsin inhibitor (BPTI)] using a heterobifunctional crosslinker (SPDP). In this initial study H-(Ala)20-Tyr-Cys-CONH2 and H-(Ala)10-Tyr-Cys-CONH2 were selected as hydrophobic peptides, since alanine is the simplest alpha-helix-forming amino acid, and the peptides as alpha-helices are just long enough to span the lipid bilayer and monolayer, respectively. The carrier protein was treated with sigma-methylisourea, which resulted in the guanidination of the four lysine epsilon-amine groups. The chemical modification of BPTI to give G-BPTI allowed the attachment of SPDP specifically to the free N-terminal alpha-amine group. The peptides were synthesized with a C-terminal cysteine moiety, allowing the site-specific cross-linking of the peptides to the N-terminus. In order to prevent peptide aggregation, the synthetic peptides were cleaved from the preparative resin in detergent and cross-linked to G-BPTI. After cross-linking, the detergent was removed from the mixture by gel filtration employing propionic and formic acids in the mobile phase. The detergent-free, peptide--G-BPTI conjugates were subsequently purified by reversed-phase HPLC. The interaction parameters of the two semisynthetic proteins with large unilamellar vesicles were determined by ultracentrifugation of the equilibrated vesicle--protein mixtures. For comparison, the same semisynthetic proteins were reconstituted into lipid vesicles using an octyl glucoside dilution technique. The incorporation and reconstitution data proved to be quite similar. The results indicated that (Ala)20--G-BPTI interacted with LUV to form a stable complex and behaved as a membrane protein in reconstituted bilayer systems. (Ala)10--G-BPTI, however, remained in the aqueous phase in both bilayer systems. The thermodynamic interaction data are compared to the theoretical values of total free energy changes calculated for the incorporation of model hydrophobic alpha-helices. In addition, the solubility and stability of the hydrophobic peptides, both in the aqueous phase and membrane-bound, were studied by cleaving the disulfide bond linking the peptides to G-BPTI using dithiothreitol. Molecular sieve chromatography was used to evaluate the state of self-association of the semisynthetic proteins in aqueous solutions.
Aprotinin↗
A possible mechanism for vesicle formation by extrusion.
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Emulsions↗
Reorganization of lipid domain structure in membranes by a transmembrane peptide: an ESR spin label study on the effect of the Escherichia coli outer membrane protein A signal peptide on the fluid lipid domain connectivity in binary mixtures of dimyristoyl phosphatidylcholine and distearoyl phosphatidylcholine.
The effect of a transmembrane peptide on the domain structure of a two-component, two-phase lipid bilayer composed of dimyristoyl phosphatidylcholine (DMPC) and distearoyl phosphatidylcholine (DSPC) was examined by spin label electron spin resonance (ESR) spectroscopy. The peptide, pOmpA, is the hydrophobic, 25-residue signal sequence of the outer membrane protein A from Escherichia coli. Nitroxide derivatives of the phospholipid DSPC, 16-DSPCSL, and of the pOmpA signal peptide, pOmpA-IASL, were used as probes. The first-derivative lineshapes of the ESR spectra were analyzed using a normalized intensity ratio, R, that gives information on the average sizes of the disconnected fluid domains and their point of connectivity (Sankaram, M.B., D. Marsh, and T.E. Thompson. 1992. Biophys. J. 63:340-349). In the absence of the peptide, the number of fluid lipid domains does not vary with the fraction of lipid that is in the fluid phase, and phase conversion is accomplished solely by changes in the domain size. The phase boundaries of the lipid mixture remain largely unchanged by the presence of the peptide at mole fractions up to 0.02, but both the size and number of the fluid domains is changed, and the point at which they become connected is shifted to lower fractions of the fluid phase. In addition, the number of domains in the presence of the peptide no longer remains constant but increases from a domain density at low fractions of the fluid phase that is much lower than that in the absence of peptide to one that is comparable to the natural state in the absence of peptide at the point of domain connectivity. A simple model is presented for the process of domain fission, where the latter is determined by a balance between the effects of peptide concentration in the fluid domains, the line tension at the domain boundaries, and the distributional entropy of the domains.
Amino Acid Sequence↗