Temperature-dependent micellar structures in poly(styrene-b-isoprene) diblock copolymer solutions near the critical micelle temperature

The temperature dependence of the micelle structures formed by poly(styrene-b-isoprene) (SI) diblock copolymers in the selective solvents diethyl phthalate (DEP) and tetradecane (C14), which are selective for the PS and PI blocks, respectively, have been investigated by small angle neutron scattering (SANS). Two nearly symmetric SI diblock copolymers, one with a perdeuterated PS block and the other with a perdeuterated PI block, were examined in both DEP and C14. The SANS scattering length density of the solvent was matched closely to either the core or the corona block. The resulting core and corona contrast data were fitted with a detailed model developed by Pedersen and co-workers. The fits provide quantitative information on micellar characteristics such as aggregation number, core size, overall size, solvent fraction in the core, and corona thickness. As temperature increases, the solvent selectivity decreases, leading to substantial solvent swelling of the core and a decrease in the aggregation number and core size. Both core and corona chains are able to relax their conformations near the critical micelle temperature due to a decrease in the interfacial tension, even though the corona chains are always under good solvent conditions.     

A scattering study on intermicellar interactions and structures of polymeric micelles

The micellar structure is usually considered to be composed of a hard sphere (liquid) core and a heavily solvated corona. Therefore, the correction for intermicellar interactions at finite concentrations can be relatively complicated. In this article, small-angle neutron scattering of a copolymer, known as Pluronic L64 (PEO₁₃PPO₃₀PEO₁₃), in o-xylene in the presence of D₂O is used to demonstrate that, based on the hard sphere approximation, intermicellar interactions can be corrected by representing the micellar size as having an equivalent hard sphere radius. The procedure remains valid even if the micellar shape becomes asymmetric, with axial ratios of 3 ? 4. For the present system, the equivalent hard sphere radius corresponds to the micellar core radius plus one-half of the micellar shell thickness. With the equivalent hard sphere approach, the scattering behavior of the micelle could be described by using a core-shell structure. © 1994 John Wiley & Sons, Inc.     

Oil-in-water microemulsions stabilized by charged diblock copolymers

We present here oil-in-water microemulsions stabilized by charged diblock copolymers alone, along with their structural characterization by small-angle neutron scattering measurements. They consist of swollen spherical micelles containing small amounts of oil in their core, which is surrounded by a corona of stretched polyelectrolyte chains. Structural changes, including core size variations, are evidenced when using a cosurfactant, or upon addition of salt, through a contraction of the charged corona. Attempts to relate the micellar structure to the individual copolymer characteristics are also presented, and show that the size of the hydrophobic block mainly determines that of the micelles.     

Structure and interactions of block copolymer micelles of Brij 700 studied by combining small-angle X-ray and neutron scattering

Spherical micelles of the diblock copolymer/surfactant Brij 700 (C(18)EO(100)) in water (D(2)O) solution have been investigated by small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). SAXS and SANS experiments are combined to obtain complementary information from the two different contrast conditions of the two techniques. Solutions in a concentration range from 0.25 to 10 wt % and at temperatures from 10 to 80 degrees C have been investigated. The data have been analyzed on absolute scale using a model based on Monte Carlo simulations, where the micelles have a spherical homogeneous core with a graded interface surrounded by a corona of self-avoiding, semiflexible interacting chains. SANS and SAXS data were fitted simultaneously, which allows one to obtain extensive quantitative information on the structure and profile of the core and corona, the chain interactions, and the concentration effects. The model describes the scattering data very well, when part of the EO chains are taken as a "background"contribution belonging to the solvent. The effect of this becomes non-negligible at polymer concentrations as low as 2 wt %, where overlap of the micellar coronas sets in. The results from the analysis on the micellar structure, interchain interactions, and structure factor effects are all consistent with a decrease in solvent quality of water for the PEO block as the theta temperature of PEO is approached.     

Size and shape of detergent micelles determined by small-angle X-ray scattering

We present a systematic analysis of the aggregation number and shape of micelles formed by nine detergents commonly used in the study of membrane proteins. Small-angle X-ray scattering measurements are reported for glucosides with 8 and 9 alkyl carbons (OG/NG), maltosides and phosphocholines with 10 and 12 alkyl carbons (DM/DDM and FC-10/FC-12), 1,2-dihexanoyl-sn-glycero-phosphocholine (DHPC), 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG), and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). The SAXS intensities are well described by two-component ellipsoid models, with a dense outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core. These models provide an intermediate resolution view of micelle size and shape. In addition, we show that Guinier analysis of the forward scattering intensity can be used to obtain an independent and model-free measurement of the micelle aggregation number and radius of gyration. This approach has the advantage of being easily generalizable to protein-detergent complexes, where simple geometric models are inapplicable. Furthermore, we have discovered that the position of the second maximum in the scattering intensity provides a direct measurement of the characteristic head group-head group spacing across the micelle core. Our results for the micellar aggregation numbers and dimensions agree favorably with literature values as far as they are available. We de novo determine the shape of FC-10, FC-12, DM, LPPG, and CHAPS micelles and the aggregation numbers of FC-10 and OG to be ca. 50 and 250, respectively. Combined, these data provide a comprehensive view of the determinants of micelle formation and serve as a starting point to correlate detergent properties with detergent-protein interactions.     

Detailed structure of hairy mixed micelles formed by phosphatidylcholine and PEGylated phospholipids in aqueous media

Aqueous dispersions of mixed egg yolk phosphatidylcholine (PC) and poly(ethylene glycol) (PEG) modified distearoyl phosphatidylethanolamine (DSPE) were investigated with the purpose of determining shape, size, and conformation of the formed mixed micelles. The samples were prepared at a range of DSPEPEG to PC molar ratios ([DSPEPEG/PC] from 100:0 to 30:70) and with, respectively, DSPEPEG2000 and DSPEPEG5000, where 2000 and 5000 refer to the molar masses of the PEG chains. Particle shape and internal structure were studied using small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The contrast of the micelles is different for X-rays and neutrons, and by combining SANS and SAXS, complementary information about the micelle structure was obtained. The detailed structure of the micelles was determined in a self-consistent way by fitting a model for the micelles to SANS and SAXS data simultaneously. In general, a model for the micelles with a hydrophobic core, surrounded by a dense hydrophilic layer that is again surrounded by a corona of PEG chains in the form of Gaussian random coils attached to the outer surface, is in good agreement with the scattering data. At high DSPEPEG contents, nearly spherical micelles are formed. As the PC content increases the micelles elongate, and at a DSPEPEG/PC ratio of 30:70, rodlike micelles longer than 1000 angstroms are formed. We demonstrate that by mixing DSPEPEG and PC a considerable latitude in controlling the particle shape is obtained. Our results indicate that the PEG chains in the corona are in a relatively unperturbed Gaussian random coil conformation even though the chains are far above the coil-coil overlap concentration and, therefore, interpenetrating. This observation in combination with the observed growth behavior questions that the "mushroom-brush"transition is the single dominating factor for determining the particle shape as assumed in previous theoretical work (Hristova, K.; Needham, D. Macromolecules 1995, 28, 991-1002).     

Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment

Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein-nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references).     

Complex coacervation core micelles. Colloidal stability and aggregation mechanism

Complex coacervation core micelles were prepared with various polyelectrolytes and oppositely charged diblock copolymers. The diblock copolymers consist of a charged block and a water-soluble neutral block. Our experimental technique was dynamic light scattering in combination with titrations. At mixing ratios where the excess charge of the polyelectrolyte mixture is approximately zero, micelles may be formed. The colloidal stability of these micelles depends on the block lengths of the diblock copolymers and the molecular weight of the homopolymers. In addition, the chemical nature of the corona blocks and nature of the ionic groups of the polyelectrolytes also influence the stability and aggregation mechanism. A corona block that is three times longer than the core block is a prerequisite for stable micelles. If this ratio is further increased, the molecular weight of the homopolymers as well as the type of the ionic groups starts to play a major role. With very asymmetric block length ratios, no micelles are formed. In addition, if the neutral block is too short, the polymeric mixture forms a macroscopic precipitate. With a constant core block, the aggregation number decreases with increasing corona block length, as is predicted by scaling models for polymeric micelles with a neutral corona.     

The effect of pharmaceuticals on the nanoscale structure of PEO-PPO-PEO micelles

We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5wt% F127 solutions were used to measure micelle core size (R(1)), micelle corona size (R(2)), intermicellar interaction distance (R(int)), polydispersity (sigma), and aggregation number (N(agg)); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle-water partition coefficient (K(mw)). The core and corona size were found to generally increase in the presence of the drugs, as did R(int). Both sigma and N(agg) were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on K(mw) in most cases. The aggregation number, however, was found to depend strongly on both K(mw) and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.     

Thermoresponsive micelles from Jeffamine-b-poly(L-glutamic acid) double hydrophilic block copolymers

Double hydrophilic block copolymers (DHBC) consisting of a Jeffamine block, a statistical copolymer based on ethylene oxide and propylene oxide units possessing a lower critical solution temperature (LCST) of 30 degrees C in water, and poly(L-glutamic acid) as a pH-responsive block were synthesized by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride using an amino-terminated Jeffamine macroinitiator, followed by hydrolysis. This DHBC proved thermoresponsive as evidenced by dynamic light scattering and small-angle neutron scattering experiments. Spherical micelles with a Jeffamine core and a poly(L-glutamic acid) corona were formed above the LCST of Jeffamine. The size of the core of such micelles decreased with increasing temperature, with complete core dehydration being achieved at 66 degrees C. Such behavior, commonly observed for thermosensitive homopolymers forming mesoglobules, is thus demonstrated here for a DHBC that self-assembles to generate thermoresponsive micelles of high colloidal stability.     

Micellar structure in gemini nonionic surfactants from small-angle neutron scattering

The size and shape of micelles formed by dimeric polyoxyethylene (nonionic gemini) surfactants having the structure (Cn-2H2n-3CHCH2(OCH2CH2)mOH)2(CH2)6 with alkyl and ethoxy chain lengths ranging from n = 12-20 and m = 5-30 have been determined using small angle neutron scattering (SANS). The surfactants are polydisperse in the hydrophilic groups but otherwise analogous to the widely studied monomeric poly(oxyethylene) alkanols. We find that longer ethoxylated chains are needed to confer solubility on the gemini surfactants and that these chains in the hydrophilic corona around the alkyl core of the micelles are reasonably well described as a homogeneous random coil in a good solvent. Spherical micelles are formed by the surfactants with the longest ethoxylated chains. Shorter chains lead first to rods and ultimately a vesicle dispersion. These solutions exhibit conventional cloud point behavior, and on warming, a sphere to rod transition can be observed. For the n = 20 and m = 15 surfactant, this shape transition is accompanied by a striking increase in viscosity at low concentration and gelation at higher concentrations.     

Entropic effects in mixed micelles formed by star/linear and star/star AB copolymers

The entropic effects in the comicellization behavior of amphiphilic AB copolymers differing in chain architecture of solvophilic A or solvophobic B parts are studied by means of molecular dynamics simulations. In particular, we studied linear/star and star/star copolymer mixtures. The properties of interest were the critical micelle concentration, the mean aggregation number, the shape of the micelle, which is expressed by the shape anisotropy, the thickness of the corona, and the solvophobic core radius. We found that the critical micelle concentration values for linear/star and copolymer mixtures show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This could be attributed to the effective interactions between copolymers originated from the architectural asymmetry. The effective interactions induce a small decrease in the aggregation number of preferential micelles in linear/star mixtures triggering the nonrandom mixing between the solvophilic moieties in the corona for all mixtures. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 442–452     

Micelles of imidazolium-functionalized polystyrene diblock copolymers investigated with neutron and light scattering

We synthesize a series of block copolymers comprising a polystyrene (PS) block and an imidazolium-functionalized PS (IL) block and characterize their assembly properties. We use small-angle neutron scattering and dynamic light scattering to determine the micelle size and shape in dilute solutions and to assess the micelle interactions in concentrated solutions. By studying a series of copolymers with fixed PS block length, we find that the length of the IL block governs the micelle dimensions. Our data suggest that these copolymers form elongated micelle structures where the IL block is extended in the micelle core. We find that these micelles can sequester water and that interactions between the micelles lead to structure factor peaks at elevated concentrations.     

Modeling detergent organization around aquaporin-0 using small-angle X-ray scattering

Solubilization of integral membrane proteins in aqueous solutions requires the presence of amphiphilic molecules like detergents. The transmembrane region of the proteins is then surrounded by a corona formed by these molecules, ensuring a hydrophilic outer surface. The presence of this corona has strongly hampered structural studies of solubilized membrane proteins by small-angle X-ray scattering (SAXS), a technique frequently used to monitor conformational changes of soluble proteins. Through the online combination of size exclusion chromatography, SAXS, and refractometry, we have determined a precise geometrical model of the n-dodecyl β-d-maltopyranoside corona surrounding aquaporin-0, the most abundant membrane protein of the eye lens. The SAXS data were well-fitted by a detergent corona shaped in an elliptical toroid around the crystal structure of the protein, similar to the elliptical shape recently reported for nanodiscs (Skar-Gislinge et al. J. Am. Chem. Soc. 2010, 132, 13713-13722). The torus thickness determined from the curve-fitting protocol is in excellent agreement with the thickness of a lipid bilayer, while the number of detergent molecules deduced from the volume of the torus compares well with those obtained on the same sample from refractometry and mass analysis based on SAXS forward scattering. For the first time, the partial specific volume of the detergent surrounding a protein was measured. The present protocol is a crucial step toward future conformational studies of membrane proteins in solution.     

Shape-persistent macrocycles: building blocks for complex organic and polymeric architectures

Alkyl- and Oligostyrene substituents were attached to shape-persistent macrocycles based on a phenyl-ethynyl backbone. In good solvents for both the rigid core and the flexible corona no aggregation occurred. Whereas, addition of a solvent that selectively solubilizes the corona induced a solvophobic aggregation. For alkyl substituted rings the experimental data were described by a monomer-dimer equilibrium. In contrast, the oligostyrene substituted rings formed more expanded aggregates which were investigated by scattering and by imaging methods. The superstructures are consequently described as hollow supramolecular cylindrical brushes.     

Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic (PEO–PPO–PEO) block copolymers

Pluronic^® block copolymers are commercially available symmetric triblock copolymers with poly(ethylene oxide), PEO, as the hydrophilic end blocks and poly(propylene oxide), PPO, as the hydrophobic middle block. In this paper, the solubilization of hydrocarbons by aggregates of Pluronic^® block copolymers in water is examined in the framework of a simple molecular theory of solubilization. The aggregates have an inner core region made up of PPO and the solubilizate and an outer corona region made up of PEO and water. Expressions for the standard state free energy change associated with solubilization of hydrocarbons by aggregates having spherical, cylindrical, and lamellar shapes are presented. These free energy contributions account for the mixing of the core block with the solubilizate, the consequent changes in the state of deformation of the core block, the changes in the state of dilution and deformation of the corona block, the formation of the core-solvent interface, and the backfolding of the triblock copolymer which ensures that the two end blocks are in contact with the solvent. Utilizing these free energy expressions, we predict the core size, the corona thickness, and the aggregation number of the micelle and also the volume fraction of the hydrocarbon solubilized in the core, for seven aromatic and aliphatic hydrocarbon solubilizates incorporated within numerous Pluronic^® compounds. The calculated results show that a growth in aggregate size occurs both because of the incorporation of the hydrocarbon and also the increase in the intrinsic number of block copolymer molecules per aggregate. More interestingly, solubilization is shown to induce a transition in aggregate shapes from spheres to cylinders and then to lamellae. The shape transition is found to be critically controlled by the free energy of mixing of the solubilizate with the core forming PPO block.     

Dendrimer-influenced supramolecular structure formation of block copolymers

The water content-dependent supramolecular structure formation of polystyrene-block-poly(acrylic acid) (PS-b-PAA) copolymer in the presence of a fourth-generation amine-terminated poly(amido amine) dendrimer (PAMAM) is investigated by dynamic light scattering, turbidity measurements, and transmission electron microscopy. The solvent system for this study is a mixture of dioxane/THF and water. A very complex turbidity profile is observed with increasing water content in the system and is explained by the presence of various aggregated structures based on strong interactions between the amine-containing dendrimers and the poly(acrylic acid) blocks of the polymer. The onset of the self-assembly of single chains of PS-b-PAA (primary structure) into single and multiple dendrimer core inverse micelles (secondary structure) is detected as very low water contents of cw < 2% wt (cwc). These micelles consist of dendrimers coated with PAA blocks, which are connected to the corresponding PS chains that form the corona. Further addition of water leads to an association of these micelles into compound multiple dendrimer core inverse micelles (tertiary structure) in the range of cw = approximately 6 to approximately 10% wt. At still higher water content, some of the acrylic acid chains of the block copolymer move from the vicinity of the dendrimer to the outside of the aggregates, resulting in a decrease in the size of the formed structures and the acquisition of progressively increasing hydrophilic character of the aggregates. Multiple dendrimer core inverse onion micelles are formed, which agglomerate into compound multiple dendrimer core inverse onion micelles at cw = approximately 12 to approximately 18% wt. Above this water content, vesicular structures are formed. The complexity is unusual for block copolymer systems and illustrates the importance of strong interactions in structure formation.     

Lattice Monte Carlo simulations of phase separation and micellization in supercritical CO2/surfactant systems: effect of CO2 density

Lattice Monte Carlo simulations are used to study the effect of nonionic surfactant concentration and CO2 density on the micellization and phase equilibria of supercritical CO2/surfactant systems. The interaction parameter for carbon dioxide is obtained by matching the critical temperature of the model fluid with the experimental critical temperature. Various properties such as the critical micelle concentration and the size, shape, and structure ofmicelles are calculated, and the phase diagram in the surfactant concentration-CO2 density space is constructed. On increasing the CO2 density, we find an increase in the critical micelle concentration and a decrease in the micellar size; this is consistent with existing experimental results. The variation of the micellar shape and structure with CO2 density shows that the micelles are spherical and that the extension of the micellar core increases with increasing micellar size, while the extension of the micellar corona increases with increasing CO2 density. The predicted phase diagram is in qualitative agreement with experimental phase diagrams for nonionic surfactants in carbon dioxide.     

Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles

It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.     

Characterization of the core-shell nanoparticles formed as soluble hydrogen-bonding interpolymer complexes at low pH

The formation of soluble hydrogen-bonding interpolymer complexes between poly(acrylic acid) (PAA) and poly(acrylic acid-co-2-acrylamido-2-methyl-1-propane sulfonic acid)-graft-poly(N,N-dimethylacrylamide) (P(AA-co-AMPSA)-g-PDMAM) at pH=2.0 was studied. A viscometric study showed that in semidilute solution a physical gel is formed due to the interconnection of the anionic P(AA-co-AMPSA) backbone of the graft copolymer, in a transient network, by means of the complexes formed between the PDMAM side chains of the graft copolymer and PAA. Dynamic and static light scattering measurements, in conjunction with small-angle neutron scattering measurements, suggest the formation of core-shell colloidal nanoparticles in dilute solution, comprised by an insoluble PAA/PDMAM core surrounded by an anionic P(AA-co-AMPSA) corona. Even if larger clusters are formed in semidilute solution, the size of the insoluble core remains practically stable. Atomic force microscopy performed under ambient conditions reveal that the particles collapse and flatten upon deposition on a substrate, with dimensions close to the ones of the dry hydrophobic core.