Complexes of Charged-Neutral Block Copolymers and Surfactants: Process-Dependent Features and Long-Term Stability of Their Aqueous Dispersions.

Aqueous dispersions of charged-neutral block copolymers (poly(acrylamide)-b-poly(acrylate)) complexed with an oppositely charged surfactant (dodecyltrimethylammonium) have been prepared by different approaches: the simple mixing of two solutions (MS approach) containing the block copolymer and surfactant, with their respective simple counterions, and dispersion of a freeze-dried complex salt prepared in the absence of simple counterions (CS approach). The CS particles were investigated under different conditions: dispersion of a CS in salt-free water and dispersion of a CS in a dilute salt solution, the latter condition yielding dispersions with the same composition as the MS process. Additionally, aged dispersions (up to 6 months) and dispersed complexes of the polyacrylate homopolymer and dodecyltrimethylammonium surfactant were evaluated. By employing different characterization techniques, it was seen that dispersions prepared by the MS approach display nanometric spherical particles with disordered cores, and poor colloidal stability, partially caused by the absence of surface charge (ζ-potential close to zero). Oppositely, anisometric particles were formed in CS dispersions and were large enough to sustain micellar cubic cores. The CS particles presented long-time colloidal stability, partially due to a net negative surface charge, but the stability varied with the length of the neutral block composing the corona. Our results demonstrate that all dispersed particles are metastable structures, with physicochemical properties strongly dependent on the preparation procedure, thus making these particles suitable for fundamental studies and potential applications where accurate control of their properties, including size, shape, internal structure, and stability, is desired.

Uncommon Structures of Oppositely Charged Hyaluronan/Surfactant Assemblies under Physiological Conditions.

Self-assembled aggregates formed by semidilute polyanion hyaluronan (hyaluronic acid, HA) and an oppositely charged surfactant tetradecyltrimethylammonium bromide (TTAB) in an aqueous phosphate-buffered saline (PBS) solution have been studied via light scattering (LS), small-angle neutron scattering (SANS), and cryogenic transmission electron microscopy (cryo-TEM). The addition of 0-20 mM TTAB to a 27.7 mM (monomer, 1 wt %) HA solution (597 kDa) in PBS buffer leads to soluble complexes until phase separation occurs near charge equilibrium (>20 mM TTAB). While the viscosity remains rather constant, already small amounts of added TTAB lead to the formation of large globular superstructures, which are built in a hierarchical fashion from a locally threadlike structural arrangement of TTA micelles along the stiff HA chains, within the little changed HA network. These globular domains have radii of 60-100 nm and contain 500-700 TTA micelles, which means that they are very "fluffy" and composed of about 99% water. They do not grow in size or number upon further TTAB addition, but, instead, the additional TTA micelles form further threadlike complexes outside of the big globular domains. Such a type of polyelectrolyte-surfactant complexes (PESCs) has not been described before and has to be attributed to the particular properties of HA, which are high stiffness and relatively weak interactions with oppositely charged micelles due to having the charged carboxylic group close to the polysaccharide backbone. These findings demonstrate that the HA network structure in solution basically remains unaffected by complexation with an oppositely charged surfactant, explaining the unchanged rheological behavior and the formation of a unique PESC local "coacervate" structure within the HA hydrogel network.

Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions.

Multiple sclerosis (MS) is an autoimmune disease, leading to the destruction of the myelin sheaths, the protective layers surrounding the axons. The etiology of the disease is unknown, although there are several postulated environmental factors that may contribute to it. Recently, myelin damage was correlated to structural phase transition from a healthy stack of lamellas to a diseased inverted hexagonal phase as a result of the altered lipid stoichiometry and low myelin basic protein (MBP) content. In this work, we show that environmental conditions, such as buffer salinity and temperature, induce the same pathological phase transition as in the case of the lipid composition in the absence of MBP. These phase transitions have different transition points, which depend on the lipid's compositions, and are ion specific. In extreme environmental conditions, we find an additional dense lamellar phase and that the native lipid composition results in similar pathology as the diseased composition. These findings demonstrate that several local environmental changes can trigger pathological structural changes. We postulate that these structural modifications result in myelin membrane vulnerability to the immune system attacks and thus can help explain MS etiology.

Sponge Phases and Nanoparticle Dispersions in Aqueous Mixtures of Mono- and Diglycerides.

The lipid liquid crystalline sponge phase (L3) has the advantages that it is a nanoscopically bicontinuous bilayer network able to accommodate large amounts of water and it is easy to manipulate due to its fluidity. This paper reports on the detailed characterization of L3 phases with water channels large enough to encapsulate bioactive macromolecules such as proteins. The aqueous phase behavior of a novel lipid mixture system, consisting of diglycerol monooleate (DGMO), and a mixture of mono-, di- and triglycerides (Capmul GMO-50) was studied. In addition, sponge-like nanoparticles (NPs) stabilized by Polysorbate 80 (P80) were prepared based on the DGMO/GMO-50 system, and their structure was correlated with the phase behavior of the corresponding bulk system. These NPs were characterized by dynamic light scattering (DLS), cryo-transmission electron microscopy (Cryo-TEM) and small angle X-ray scattering (SAXS) to determine their size, shape, and inner structure as a function of the DGMO/GMO-50 ratio. In addition, the effect of P80 as stabilizer was investigated. We found that the NPs have aqueous pores with diameters up to 13 nm, similar to the ones in the bulk phase.

Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis.

In demyelinating diseases such as multiple sclerosis, disrupted myelin structures impair the functional role of the sheath as an insulating layer for proper nerve conduction. Though the etiology and recovery pathways remain unclear, in vivo studies show alterations in the lipid and the adhesive protein (myelin basic protein, MBP) composition. We find that in vitro cytoplasmic myelin membranes with modified lipid composition and low MBP concentration, as in demyelinating disease, show structural instabilities and pathological phase transition from a lamellar to inverted hexagonal, which involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. In addition, MBP dimers form a correlated mesh-like network within the inner membrane space, only in the vicinity of native lipid composition. These findings delineate the distinct functional roles of dominant constituents in cytoplasmic myelin sheaths, and shed new light on mechanisms disrupting lipid-protein complexes in the diseased state.

Effect of Polyelectrolyte Stiffness and Solution pH on the Nanostructure of Complexes Formed by Cationic Amphiphiles and Negatively Charged Polyelectrolytes.

The interaction between amphiphiles and polyelectrolytes has been widely investigated in recent years due to their potential application in industry and medicine, with special focus on gene therapy. The cationic lipid dioleoyl trimethylammonium propane, DOTAP, and the oppositely charged polyelectrolytes, sodium poly(acrylic acid) and sodium poly(styrenesulfonate), form multilamellar complexes in water. Because of the different molecular stiffness of the two polyelectrolytes, they form different nanostructured complexes. Also, because of the different ionization behavior of the two polyelectrolytes, pH differently affects the complexation of the polyelectrolytes with didodecyldimethylammonium bromide (DDAB), another cationic surfactant. We used cryogenic temperature transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) to compare the nanostructures formed. Our results show that although the basic nanostructures of the complexes are always lamellar (multilamellar or unilamellar) the morphology of the complexes is affected by the polyelectrolyte rigidity and the solution pH.