Competition among physical, chemical, and hybrid gelation mechanisms in biopolymers.

Depending on how they form their linkages, biopolymer gelatin gels are commonly classified as physical, chemical, or hybrid; in gelatin hybrid gels, the physical and chemical crosslinking mechanisms occur simultaneously. The viscoelastic behavior of gels following different gelation processes was determined around the gel point. Their gel fractal dimensions were obtained using the BST-scaling model from large amplitude oscillatory shear results. The fractal dimension of hybrid gels is between 1.46 and 1.60, depending on the dominant crosslinking process. The main features of the Lissajous-Bowditch curves were determined for maturated gels that follow different gelation processes, and it is possible to observe the dominant gelation mechanism. The gelation kinetics process is followed by measuring the mean squared displacement (MSD) of microspheres embedded in gelatin solutions using diffusion wave spectroscopy, which in turn allows evaluating G'(ω) and G''(ω), the persistence length, and the mesh size as a function of time throughout the gelation process. The MSD, as a function of elapsed time from the start of the gelation process, follows a behavior that depends on the gelation processes. As time elapses after gelation starts, the persistence length of the unstructured, non-bonded flexible polymer sections decreases due to the formation of bonds. In the hybrid case, it is not a mixture of both processes; they are not independent when occurring simultaneously. The time evolution of the gel network's mesh size roughly follows an exponential decay.

Mie scattering theory applied to light scattering of large nonhomogeneous colloidal spheres.

Colloidal suspensions made of smart core-shell structures are of current interest in many fields. Their properties come from the possibility of varying the core and shell materials for modifying the composite particles' chemical, biological, and optical properties. These particles are formed with a material with a constant refractive index core and a shell with a refractive index decaying until it matches the solvent refractive index. Poly(N-IsoPropyl AcrylaMide) (PNIPAM) is a typical example of materials forming shells. In this report, we present how to apply Mie scattering theory to predict and understand the static light scattering of large nonhomogeneous colloidal particles with spherical symmetry whose size is comparable with or larger than the light wavelength used for developing scattering experiments, where the Rayleigh-Gans-Debye approximation is not valid. Here, the refractive index decay was approximated by a Gaussian RI profile numerically evaluated through a multilayer sphere. We calculated the form factor functions of suspensions of PNIPAM microgels previously reported and core-shell suspensions made of polystyrene/PNIPAM at 20 and 40 °C synthesized by us. In all the cases, our method succeeded in providing the scattering intensity as a function of the angle. The software for using the numerical method is fairly straightforward and is accessible as an open-source code. The results can not only help predict and understand the photonic properties of microgels with large core-shell structures but also for any particle with a refractive index distribution with spherical symmetry, as in the case of microgels with super chaotropic agents, hollow microgels, or microparticles.

Measurement of the capillary interaction force between Janus colloidal particles trapped at a flat air/water interface.

The capillary interaction force between spherical Janus particles trapped at the air-water interface is measured using a time-sharing optical tweezer (bond number ≪ 1). One face of the particles is hydrophilic, and the other one, hydrophobic. Measured force goes from almost pure quadrupolar to almost pure hexapolar interaction due to the three-phase contact line corrugation. Measured force curves are modeled as a sum of power laws, Ar-α + Br-ß + Cr-γ, obtained from an expansion in capillary multipoles. The mean values for the exponents of particle pairs of 3 µm are 〈α〉 = 5.05 ± 0.12, 〈ß〉 = 7.02 ± 0.03, and 〈γ〉 = 5.96 ± 0.03. For particles pairs of 5 µm, we find 〈α〉 = 5.02 ± 0.04, 〈ß〉 = 6.94 ± 0.06, and 〈γ〉 = 5.80 ± 0.05. In both cases, A < 0, B < 0, and C > 0.

Mechanical Properties of DPPC-POPE Mixed Langmuir Monolayers.

The mechanical properties of lipid monolayers and their responses to shear and compression stresses play an important role in processes such as breathing and eye blinking. We studied the mechanical properties of Langmuir monolayers of a model mixture, composed of an unsaturated lipid, 1-palmitoyl-2-oleoyl-sn-glycero-phosphoethanolamine (POPE), and a saturated lipid, 1,2-dipalmitoyl-sn-glycero-phosphocholine (DPPC). We performed isothermal compressions and sinusoidal shear deformations of these mixed monolayers. Also, the different phases were observed with Brewster angle microscopy. We found that the mechanical behavior is affected by the miscibility of both lipids. In the two-phase region, the compression elastic modulus increases with the amount of the LC phase but does not follow the predictions of a simple effective medium model. The discrepancies arise from the fact that, upon compression, the domains grow at a rate faster than the compression rate but not fast enough to reach thermodynamic equilibrium. Before reaching the LC phase, domain percolation is observed and compression and shear moduli become equal to those of the pure LC phase. Most of the monolayers behave as viscoelastic fluids at the frequencies investigated. A minimum in the compression modulus and shear viscosity was observed for mixtures close to equimolar composition, with the minimum being accompanied by a change in domain shapes.

Measurement of the force between uncharged colloidal particles trapped at a flat air/water interface.

The radial attraction between microspheres straddling at the air/water interface (Bond number ≪1), whose origin is the irregular shape of the contact line and its concomitant distortion of the water surface, is measured using two light beams of a time-sharing optical tweezer. The colloidal particles used to make the measurements are microspheres made of hydrophobically covered silica to reduce the electrostatic interactions to a minimum. The measured radial force goes as a quadrupolar power law, r-n, with n = 5.02 ± 0.18 and n = 5.04 ± 0.18 for particles of 3 µm and 5 µm, respectively. In both cases, the electrostatic interaction is negligible.

Bilayers of Janus and homogeneous particle mixtures trapped at an air/water interface.

We study mixtures of amphiphilic Janus and homogeneous hydrophobic particles trapped at an air/water interface. In contrast to an expected monolayer formation, bilayers of colloidal particles are produced. Despite their strong interfacial adsorption, Janus particles form the upper layer. They are not placed on top of the other particles but rather shifted about one-third of the particle diameter. To understand the mechanism of bilayer formation, particle behaviour at the surface and in the bulk of the spreading solvent is considered. The vertical shift and the bilayer formation are assisted by the momentous formation of two interfaces during spreading.

Structure, rheology, and microrheology of wormlike micelles made of PB-PEO diblock copolymers.

A diblock copolymer made of poly(1,4-butadiene)-block-polyethylene oxide, with a degree of polymerization of the polybutadiene and polyethylene oxide blocks of 37 and 57, respectively, self-assembles in water as worm-like micelles determined by small angle neutron scattering with an average diameter of ∼12.7 nm, a core radius of ∼2.7 nm, a shell radius of ∼3 nm, and an estimated persistence length of >225 nm. Worm-like micelles of almost the same diblock copolymer, but with a smaller polyethylene oxide block (degree of polymerization 45) were also measured. The worm-like micelles were also observed with negative staining using low energy electron microscopy. The boundary between dilute and semidilute regimes was estimated to be ∼0.8 wt%. The viscoelastic spectra at low and intermediate frequencies do not follow the Maxwell model. These micelles do not present the same rheological behavior of worm-like micelle solutions of conventional surfactants. The slow dynamics of the self-assembly explains this uncommon behavior for the system. Any micellar rearrangement is impeded due to the extremely high hydrophobicity of the polybutadiene block; stress mainly relaxes by the reptation mechanism. Using diffusive wave spectroscopy, we measured the mean square displacement of particles in the micellar solution. From the mean square displacement, we obtained G'(ω) and G''(ω) at high frequencies. |G*| exhibits a power law behavior showing the stress relaxation changes as frequency increases, first dominated by the Rouse-Zimm modes and then by the bending modes of the Kuhn segments. This allowed us to estimate the worm-like micelle persistence lengths that depend on the copolymer concentration.

Microenvironmentally controlled secondary structure motifs of apolipoprotein A-I derived peptides.

The structure of apolipoprotein A-I (apoA-I), the major protein of HDL, has been extensively studied in past years. Nevertheless, its corresponding three-dimensional structure has been difficult to obtain due to the frequent conformational changes observed depending on the microenvironment. Although the function of each helical segment of this protein remains unclear, it has been observed that the apoA-I amino (N) and carboxy-end (C) domains are directly involved in receptor-recognition, processes that determine the diameter for HDL particles. In addition, it has been observed that the high structural plasticity of these segments might be related to several amyloidogenic processes. In this work, we studied a series of peptides derived from the N- and C-terminal domains representing the most hydrophobic segments of apoA-I. Measurements carried out using circular dichroism in all tested peptides evidenced that the lipid environment promotes the formation of α-helical structures, whereas an aqueous environment facilitates a strong tendency to adopt ß-sheet/disordered conformations. Electron microscopy observations showed the formation of amyloid-like structures similar to those found in other well-defined amyloidogenic proteins. Interestingly, when the apoA-I peptides were incubated under conditions that promote stable globular structures, two of the peptides studied were cytotoxic to microglia and mouse macrophage cells. Our findings provide an insight into the physicochemical properties of key segments contained in apoA-I which may be implicated in disorder-to-order transitions that in turn maintain the delicate equilibrium between both, native and abnormal conformations, and therefore control its propensity to become involved in pathological processes.

Worm-like micelles in water solutions of 1, 4 poly (1, 3-butadiene)-polyethylene oxide diblock copolymer.

The main purpose of this study is to determine for the first time the structure of the self-assembled aggregates in the system made of 1,4 poly(1,3-butadiene)-polyethylene oxide diblock copolymer (IUPAC name: poly(but-2-ene-1,4-diyl)-block-polyoxyethylene) and water, and the rheological behavior of the solution. The degree of polymerization of the polybutadiene and polyethylene oxide blocks is 37 and 45, respectively. The diblock copolymer concentration was limited to be ≤2.5 wt% to avoid phase separation. Small X-ray scattering revealed that the diblock copolymer self-assembles in worm-like micelles with a diameter of ∼ 12 nm. This system does not closely follow the rheological behavior of worm-like micelle solutions made of typical surfactants. The system steadily shear thins reaching very low viscosity values at large shear rates, however there are not shear-thickening peaks. In thixotropic loops, the micellar solution does not present hysteresis. The viscoelastic spectra do not follow the Maxwell model at low and intermediate frequencies. This uncommon behavior for a worm-like micellar system is explained by the slow dynamics of the self-assembly. The extremely high hydrophobicity of the polybutadiene block does not allow any micellar rearrangement.

Absorption effects in diffusing wave spectroscopy.

The effect of absorption in diffusing wave spectroscopy (DWS) was studied using an absorption-dependent diffusive equation for describing the light propagation within a turbid liquid where dielectric microspheres have been embedded. Here, we propose an expression for the time-averaged light intensity autocorrelation function that correctly describes the time fluctuations for the scattered light, in the regime where the diffusion approximation accurately describes the light propagation. This correction was suspected previously, but it was not formally derived from a light diffusive equation. As in the case of no absorption, we obtained that time fluctuations of the scattered light can be related to the mean square displacement of the embedded particles. However, if a correction for absorption is not taken into account, the colloidal dynamics can be misinterpreted. Experimental results show that this new formulation correctly describes the time fluctuations of scattered light. This new procedure extends the applicability of DWS, and it opens the possibility of doing microrheology with this optical method in systems where absorption cannot be avoided.

Force of adhesion upon loss of contact angle hysteresis: when a liquid behaves like a solid.

The theoretically predicted vanishment of the macroscopic contact angle hysteresis is found experimentally along with a small but finite force of adhesion (F(Ad)≈-0.5 µN) that, unexpectedly, is independent of the history of the preload. Our results agree with the prediction of a model in which the surface tension of the liquid provides the counterpart of the restoring force of an elastic solid, evidencing that the dewetting of a liquid in the absence of strong pinning points is equivalent to the detachment of an elastic solid.

Bioassay-guided isolation and identification of cytotoxic compounds from Gymnosperma glutinosum leaves.

Bioassay-guided fractionation of hexane extracts of Gymnosperma glutinosum (Asteraceae) leaves, collected in North Mexico, afforded the known compounds hentriacontane (1) and (+)-13S,14R,15-trihydroxy-ent-labd-7-ene (2), as well as the new ent-labdane diterpene (-)-13S,14R,15-trihydroxy-7-oxo-ent-labd-8(9)-ene (3). In addition, D-glycero-D-galactoheptitol (4) was isolated from the methanolic extract of this plant. Their structures were established on the basis of high-field 1D- and 2D NMR methods supported by HR-MS data. The cytotoxic activity was determined by using the in vitro L5178Y-R lymphoma murine model. Hentriacontane (1) and the new ent-labdane 3 showed weak cytotoxicity, whereas the ent-labdane 2 showed significant (p < 0.05) and concentration dependent cytotoxicity (up to 78%) against L5178Y-R cells at concentrations ranging from 7.8 to 250 µg/mL.

Micellar entanglement and its relation to the elastic behavior of wormlike micelle fluids.

HYPOTHESIS: The elastic contribution to the fluid dynamics of wormlike micellar solutions makes these fluids unique due to the distinctive self-assembled micellar network formed by tubular micelles. Measured mesoscopic scales of the micellar network related to the degree of entanglement can give guidelines for understanding the origin of elastic forces and their effect on rheological response. EXPERIMENTS: Different experiments were made as flow curves, rotating the internal or external cylinder in a Couette geometry, small and large oscillatory shear tests, and linear shear banding observations, all of them to determine how elastic forces modify the rheological behavior in systems made of different ratios of hexadecyltrimethylammonium bromide (CTAB)/sodium salicylate (NaSal) and different ratios of CTAB/NaNO3. Diffusive wave spectroscopy micro-rheology was also performed to measure the mean square displacements of microspheres embedded in the micellar fluids to obtain their high-frequency viscoelastic spectra. With this information, the entanglement index κ, the ratio of the total contour of the micelles to the entanglement length, was estimated and correlated with the rheological behavior. FINDINGS: The entanglement index is a valuable piece of information to understand the origin of the contribution of the elastic forces from a molecular point of view on the fluid dynamics of wormlike micelle solutions.

Measuring mesoscopic scales in complex fluids embedded with giant cylindrical micelles with diffusing wave spectroscopy micro-rheology.

This review paper presents a procedure for measuring the mesoscopic scales in micellar solutions embedded with giant cylindrical micelles using the mean square displacement determined with a quasi-elastic multiple light scattering method (diffusing wave spectroscopy) and theory. The mesoscopic scales of interest are the micelles' total contour length, persistence and entanglement lengths, and the mesh size of the entangled micellar network. All of them depend on the physicochemical parameters of the solutions and determine the rheological behavior. We present an assessment of the whole procedure, the scattering experiments performance, the recovery of optical parameters, which includes dealing with the light absorption and its treatment, and how to develop the micro-rheology for obtaining the mesoscopic scales in these complex fluids.

BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review.

Brain Derived Neurotrophic Factor (BDNF) has been linked to cognitive symptoms of schizophrenia, which has been documented in previous reviews by several authors. However, a trend has recently emerged in this field moving from studying schizophrenia as a disease to studying psychosis as a group. This review article focuses on recent BDNF studies in relation to cognition in human subjects during different stages of the psychotic process, including subjects at high risk of developing psychosis, patients at their first episode of psychosis, and patients with chronic schizophrenia. We aim to provide an update of BDNF as a biomarker of cognitive function on human subjects with schizophrenia or earlier stages of psychosis, covering new trends, controversies, current research gaps, and suggest potential future developments in the field. We found that most of current research regarding BDNF and cognitive symptoms in psychosis is done around schizophrenia as a disease. Therefore, it is necessary to expand the study of the relationship between BDNF and cognitive symptoms to psychotic illnesses of different stages and origins.

Alignment of worm-like micelles at intermediate and high shear rates.

HYPOTHESIS: Rheology combined with Small-Angle Neutron Scattering (Rheo-SANS) can determine the local structural order in Worm-Like Micelle (WLM) solutions when the shear rate increases beyond the ending of the gradient shear banding. There, micelles are supposedly aligned, but viscosity reveals a transition regime as the shear rate increases. EXPERIMENTS: The mixture of 3-[dimethyl(tetradecyl)azaniumyl]propane-1-sulfonate (TDPS), sodium dodecylsulfate (SDS) (R = [SDS]/[TDPS] = 0.55), and a water solution of NaCl (0.2 mol/L), was studied with mechanical rheology and Small-Angle Neutron Scattering (SANS) in the quiescent fluid and under flow. FINDINGS: The system self-assembles in WLMs and presents gradient shear banding. SANS patterns of the bands formed during the shear banding were obtained in a Couette geometry along the 1-2 plane, as well as the orientation parameter along the gap. At very high shear rates, in the paranematic phase, we found an apparent transition on the flow curves with its corresponding change in the orientation parameter. The origin of this transition is unclear, but we present possible explanations of why we observe it.

Disorder-to-order conformational transitions in protein structure and its relationship to disease.

Function in proteins largely depends on the acquisition of specific structures through folding at physiological time scales. Under both equilibrium and non-equilibrium states, proteins develop partially structured molecules that being intermediates in the process, usually resemble the structure of the fully folded protein. These intermediates, known as molten globules, present the faculty of adopting a large variety of conformations mainly supported by changes in their side chains. Taking into account that the mechanism to obtain a fully packed structure is considered more difficult energetically than forming partially "disordered" folding intermediates, evolution might have conferred upon an important number of proteins the capability to first partially fold and-depending on the presence of specific partner ligands-switch on disorder-to-order transitions to adopt a highly ordered well-folded state and reach the lowest energy conformation possible. Disorder in this context can represent segments of proteins or complete proteins that might exist in the native state. Moreover, because this type of disorder-to-order transition in proteins has been found to be reversible, it has been frequently associated with important signaling events in the cell. Due to the central role of this phenomenon in cell biology, protein misfolding and aberrant disorder-to-order transitions have been at present associated with an important number of diseases.

Structural Changes in Wormlike Micelles on the Incorporation of Small Photoswitchable Molecules.

Chromophores susceptible to light-induced trans-cis isomerization embedded in cylindrical micelles can modify micelles and their light-responsive performance. A small chromophore (4-(phenylazo)benzoate ion) is embedded in cylindrical micelles made of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal) in water. The microstructure is examined by scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Rheological behavior and the length scales of the micellar network are determined by rheology and microrheology. The chromophore substantially modifies the micelles even without UV irradiation. The larger is the chromophore concentration, the smaller is the micellar length. Additional length scales of the micellar network do not substantially vary even when NaCl is added. Chromophore incorporation also modifies the rheology of the micellar solution, although gradient shear banding is preserved. Viscosity decreases as the chromophore concentration increases, and viscoelastic spectra are modified, but when they are correctly rescaled, they can be superimposed. The addition of the chromophore makes the fluids more Maxwellian, particularly when NaCl is also added. When the chromophore is incorporated into the micelles, there is a response after UV irradiation, although it does not produce a significant rheological change.

Early psychosis detection program in Chile: A first step for the South American challenge in psychosis research.

AIM: Early detection and intervention (EDI) is a main challenge in psychosis research. The Chilean schizophrenia (SZ) national program has universal support and treatment by law for all SZ patients, but this does not yet extend to earlier stages of illness. Therefore, we have piloted an ultra-high risk (UHR) program to demonstrate the utility and feasibility of this public health approach in Chile. METHODS: We introduce "The University of Chile High-risk Intervention Program," which is the first national EDI program for UHR youths. Longitudinal follow-up included clinical and cognitive assessments, and monitoring of physiological sensory and cognitive indices, through electroencephalographic techniques. RESULTS: We recruited 27 UHR youths over 2 years. About 92.6% met criteria for attenuated psychosis syndrome (APS). Mean Scale of Psychosis-Risk Symptoms (SOPS) ratings in the cohort were 6.9 (SD 4.6) for positive, 9.1 (SD 8.3) for negative, 5.4 (SD 5.3) for disorganized and 6.3 (SD 4.1) for general symptoms. About 14.8% met criteria for comorbid anxiety disorders and 44.4% for mood disorders. Most participants received cognitive behavioural therapy (62.9%) and were prescribed low dose antipsychotics (85.2%). The transition rate to psychosis was 22% within 2 years. CONCLUSIONS: We describe our experience in establishing the first EDI program for UHR subjects in Chile. Our cohort is similar in profile and risk to those identified in higher-income countries. We will extend our work to further optimize psychosocial and preventive interventions, to promote its inclusion in the Chilean SZ national program and to establish a South American collaboration network for SZ research.

Lipid dependant disorder-to-order conformational transitions in apolipoprotein CI derived peptides.

In contrast to the notion established for many years that protein function depends on rigid 3D structures, nowadays there is important evidence suggesting that non-structured segments of proteins play important roles in protein function. Therefore, disorder-to-order dynamic conformational transitions have been proposed as an attractive mechanism involved in protein-protein recognition. Our laboratory using Langmuir monolayers of apolipoproteins has previously shown that upon lateral compression at the air/water and phospholipid/water interfaces, there is an important movement of the C-terminal segment of apolipoprotein CI towards the air, considered the hydrophobic region of the monolayer and the acyl-chain region of the interface when phospholipids are used. Here, in an attempt to define secondary structure changes that might occur within this C-terminal segment of apoCI while moving from the monolayer interface back and forth its hydrophobic region, employing three peptides derived from apoCI we studied by circular dichroism and dynamic light scattering their conformational properties when associated to a series of amphipathic lipids and lipid-like molecules. Our results show that a series of lysophospholipids present the ability to modulate the formation of an alpha helix at the C-terminal peptide of apoCI through a disorder-to-order transition while forming small lipid/peptide aggregates below 10nm in diameter.