Physiology and Physical Chemistry of Bile Acids di Gregorio, Maria Chiara; Cautela, Jacopo; Galantini, Luciano
International journal of molecular sciences,
02/2021, Letnik:
22, Številka:
4
Journal Article
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Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in ...the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical-physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bio-applications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science.
Bile salts (BSs) are naturally occurring rigid surfactants with a steroidal skeleton and specific self-assembly and interface behaviors. Using bile salts as precursors, derivatives can be synthesized ...to obtain molecules with specific functionalities and amphiphilic structure. Modifications on single molecules are normally performed by substituting the least-hindered hydroxyl group on carbon C-3 of the steroidal A ring or at the end of the lateral chain. This leads to monosteroidal rigid building blocks that are often able to self-organize into 1D structures such as tubules, twisted ribbons, and fibrils with helical supramolecular packing. Tubular aggregates are of particular interest, and they are characterized by cross-section inner diameters spanning a wide range of values (3–500 nm). They can form through appealing pH- or temperature-responsive aggregation and in mixtures of bile salt derivatives to provide mixed tubules with tunable charge and size. Other derivatives can be prepared by covalently linking two or more bile salt molecules to provide complex systems such as oligomers, dendrimers, and polymeric materials. The unconventional amphiphilic molecular structure imparts specific features to BSs and derivatives that can be exploited in the formulation of capsules, drug carriers, dispersants, and templates for the synthesis of nanomaterials.
Plasmonically enhanced optical dichroism has attracted substantial interest for its application in optical sensing, where the interplay between chirality emanating from both molecules and ...plasmon-supporting structures has been regarded as a critical ingredient. Here, we experimentally demonstrate that suitably self-assembled achiral plasmonic nanostructures produce a high degree of enhancement in the optical dichroism observed from chiral molecules placed in their vicinity. Specifically, we identify a near-field enhancement associated with plasmonic hotpots as the mechanism enabling our observation of visible-NIR circular dichroism emanating from small amounts of chiral molecules. Our structures consist of linear arrays of gold nanorods obtained by introducing chiral anionic surfactants, such as modified bile salts, which lead to selective destabilization of a cetyltrimethylammonium bromide coating layer on Au nanorods, thereby promoting a tip-to-tip oriented assembly. The proposed mechanism of plasmonically-enhanced circular dichroism is supported by deriving a simple, yet general theoretical formalism that confirms the observed results, revealing the role of optical hotspots at the gaps of linear tip-to-tip nanorod assemblies as the origin of enhancement in the dichroism from chiral molecules. Importantly, it is the refractive rather than the absorption-mediated chiral response of the molecules that produces dichroism in the visible-NIR plasmonic regime, far from their UV absorption resonances. The observed self-assembly mechanism suggests that chiral analytes not directly interacting with the nanorod surfaces, but just able to induce tip-to-tip aggregation, can be revealed by a CD signature in the plasmonic region, thereby supporting potential applications in ultrasensitive analysis.
Polymeric wet-strength agents are important additives used in the paper industry to improve the mechanical properties of paper products, especially when they come into contact with water. These ...agents play a crucial role in enhancing the durability, strength, and dimensional stability of paper products. The aim of this review is to provide an overview of the different types of wet-strength agents available and their mechanisms of action. We will also discuss the challenges associated with the use of wet-strength agents and the recent advances in the development of more sustainable and environmentally friendly agents. As the demand for more sustainable and durable paper products continues to grow, the use of wet-strength agents is expected to increase in the coming years.
CP12 is a redox-dependent conditionally disordered protein universally distributed in oxygenic photosynthetic organisms. It is primarily known as a light-dependent redox switch regulating the ...reductive step of the metabolic phase of photosynthesis. In the present study, a small angle X-ray scattering (SAXS) analysis of recombinant Arabidopsis CP12 (AtCP12) in a reduced and oxidized form confirmed the highly disordered nature of this regulatory protein. However, it clearly pointed out a decrease in the average size and a lower level of conformational disorder upon oxidation. We compared the experimental data with the theoretical profiles of pools of conformers generated with different assumptions and show that the reduced form is fully disordered, whereas the oxidized form is better described by conformers comprising both the circular motif around the C-terminal disulfide bond detected in previous structural analysis and the N-terminal disulfide bond. Despite the fact that disulfide bridges are usually thought to confer rigidity to protein structures, in the oxidized AtCP12, their presence coexists with a disordered nature. Our results rule out the existence of significant amounts of structured and compact conformations of free AtCP12 in a solution, even in its oxidized form, thereby highlighting the importance of recruiting partner proteins to complete its structured final folding.
To date, crystallization studies conducted in space laboratories, which are prohibitively costly and unsuitable to most research laboratories, have shown the valuable effects of microgravity during ...crystal growth and morphogenesis. Herein, an easy and highly efficient method is shown to achieve space‐like experimentation conditions on Earth employing custom‐made microfluidic devices to fabricate 2D porous crystalline molecular frameworks. It is confirmed that experimentation under these simulated microgravity conditions has unprecedented effects on the orientation, compactness and crack‐free generation of 2D porous crystalline molecular frameworks as well as in their integration and crystal morphogenesis. It is believed that this work will provide a new “playground” to chemists, physicists, and materials scientists that desire to process unprecedented 2D functional materials and devices.
How to achieve simulated microgravity conditions on Earth? The art of growing and processing 2D porous crystalline molecular frameworks in simulated microgravity is presented.
Small angle X-ray (SAXS) and neutron scattering techniques were combined to study mixed complexes formed between micelles of the nonionic amphiphilic PEO-PPO-PEO copolymer (P123) and the anionic bile ...salt (NaGDC) in aqueous solution. The purpose was to investigate the structural parameters of the charged complexes, such as size and internal structure, as well as their interparticle interactions in aqueous solution. The overall aim of this work was to gain understanding of how thermoresponsive PEO-PPO-PEO block copolymers interact with bile salts in order to make predictions as to whether they can be put forward as a new class of bile salt sequestrants in the treatment of bile-salt related diseases. The system was investigated at a constant P123 concentration of 1.74 mM and bile salt concentrations were varied up to a molar ratio n sub(NaGDC)/n sub(P123)nNaGDC/nP123 (MR) = 5.7. It was found that the NaGDC molecules preferentially associated to the PEO corona of the P123 micelle and due to their amphiphilic nature, close to the core/corona interface. Because of this association the micelles became charged causing their reciprocal interparticle repulsions in solution to increase. In parallel, the association caused a decrease in the core radius accompanied by dehydration, which in turn led to a decrease in total radius of the "P123 micelle-NaGDC" complexes. To elucidate the effect of the interactions on their diffusive motion, an interaction model based on a spherical particle with a hard-core interaction shell was employed using the fitted SAXS data. At higher molar ratios, the interparticle interaction was increasingly screened because of nonadsorbed bile salt in the surrounding solution. Meanwhile, a further decrease in total radial size of the P123 micelle-NaGDC complexes occurred due to a decrease in the aggregation number of P123 as the bile salt finally disintegrated the complexes. However, the micelles were found to be more stable and less prone to disintegration in D sub(2)O. This investigation demonstrated the importance of using small angle scattering techniques for studying intermolecular interactions in order to gain understanding of how natural surfactants influence the aggregation behavior of amphiphilic polymers.
In this work, we report on the development of a simple electrochemical immunosensor for the detection of D-dimer protein in human plasma samples. The immunosensor is built by a simple drop-casting ...procedure of chitosan nanoparticles (CSNPs) as biocompatible support, Protein A (PrA), to facilitate the proper orientation of the antibody sites to epitopes as a capture biomolecule, and the D-dimer antibody onto a carboxyl functionalized multi-walled carbon nanotubes screen printed electrode (MWCNTs-SPE). The CSNPs have been morphologically characterized by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS) techniques. Successively, the electrochemical properties of the screen-printed working electrode after each modification step have been characterized by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The resulting MWCNTs-CSNPs-PrA-D-dimer Ab immunosensor displays an optimal and promising platform for antibody immobilization and specific D-dimer detection. DPV has been used to investigate the antigen/antibody interaction at different D-dimer concentrations. The proposed voltammetric immunosensor allowed a linear range from 2 to 500 μg L
with a LOD of 0.6 μg L
and a sensitivity of 1.3 μA L μg
cm
. Good stability and a fast response time (5 s) have been reported. Lastly, the performance of the voltammetric immunosensor has been tested in human plasma samples, showing satisfactory results, thus attesting to the promising feasibility of the proposed platform for detecting D-dimer in physiological samples.
The present study investigates the utilization of nanoparticles based on poly-l-lactide (PLLA) and polyglycerol adipate (PGA), alone and blended, for the encapsulation of usnic acid (UA), a potent ...natural compound with various therapeutic properties including antimicrobial and anticancer activities. The development of these carriers offers an innovative approach to overcome the challenges associated with usnic acid's limited aqueous solubility, bioavailability, and hepatotoxicity. The nanosystems were characterized according to their physicochemical properties (among others, size, zeta potential, thermal properties), apparent aqueous solubility, and in vitro cytotoxicity. Interestingly, the nanocarrier obtained with the PLLA-PGA 50/50 weight ratio blend showed both the lowest size and the highest UA apparent solubility as well as the ability to decrease UA cytotoxicity towards human hepatocytes (HepG2 cells). This research opens new avenues for the effective utilization of these highly degradable and biocompatible PLLA-PGA blends as nanocarriers for reducing the cytotoxicity of usnic acid.
An approach for tailoring self‐assembled tubular structures is described. By controlling the relative composition of a two‐component surfactant mixture comprising the natural bile salt lithocholate ...and its bolamphiphilic derivative, it was possible to finely tune the nanotube cross‐section of the mixed tubular aggregates that self‐associated spontaneously in aqueous solution at pH 12. The diameter was found to vary up to 50 % when the stoichiometric ratio of the two bile salts was changed. The tuning of supramolecular nanochannels with such remarkable precision is of significant interest for technological applications of these materials.
The perfect fit: The tailoring of self‐assembled nanotube cross‐sections is described for two‐component mixtures of a bile acid and its derivative. By controlling the stoichiometry, diameters were found to vary by up to 50 %. Starting from pure tubules with a parallel arrangement of the monomer, a progressive inclusion of the second component in an antiparallel orientation is proposed to explain the variation in size.
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