Salt Effects in the Formation of Self-Assembled Lithocholate Helical Ribbons and Tubes

The formation of self-assembled nanotubes is usually accounted for by anisotropic elastic properties of membranelike precursors. We present experimental data as evidence of the role played by electrostatics in the formation of self-assembled tubes in alkaline aqueous suspensions of lithocholic acid (LCA). Striking salt effects are characterized by comparing the rheological, dynamical, and scattering properties of systems prepared either in stoichiometric neutralization conditions (SC) of LCA or in a large excess of sodium hydroxide (EOC, experimentally optimized conditions) and finally, in two steps: stoichiometric neutralization followed by an appropriate addition of NaCl (AISC). The SC liquid system is originally made up of loose helical ribbons (previous transmission electron microscopy data), and upon aging they exhibit both intra- and interordering processes. Initially, the helical ribbons are loose and progressively wind around a cylinder (<i>R</i> = 330 Å) with their edges exposed to the solvent. They can be temporarily organized in a centered rectangular two-dimensional lattice (<i>pgg</i>, <i>a</i> = 224 Å, <i>b</i> = 687 Å). Upon further aging, the ribbons wind into more compact helical ribbons (or tubes with helical grooves): their edges are less-exposed and their ordering vanishes. Upon addition of NaCl salt (as in the AISC systems), the specific screening of the intra-aggregate electrostatic repulsions induces the closure of the ribbons into tubes (<i>R</i>_ext = 260 Å, <i>R</i>_int = 245 Å as in the EOC systems). Simultaneously with the closure of the ribbons into plain tubes, a drastic enhancement of their interconnectivity through van der Waals attractions develops. Eventually, gels are obtained with networks having hexagonal bundles of tubes

Metallogels from a Glycolipid Biosurfactant

Low-molecular-weight (LMW) molecules of biological origin like microbial glycolipid biosurfactants can self-assemble in water, with a tunable structure by a soft chemistry approach (pH, temperature, and ionic strength). The unique molecular structure of microbial glycolipids gives possible access to a wide variety of aqueous self-assembled structures, although highly unpredictable beforehand. The glycolipid presented here consists in a glucose group linked to a C18:1-cis fatty acid (G-C18:1) and produced by the fermentation of Starmerella bombicola ΔugtB1. Due to the carboxylic group of the fatty acid, the supramolecular self-assembly is pH dependent. In the pH range 5–7, G-C18:1 forms vesicles, while above pH 7, it forms a micellar phase. Adding a wide range of metal salts (ion radius in ascending order: Al3+, Fe3+, Ni2+, Mg2+, Cu2+, Zn2+, Co2+, Fe2+, Cr2+, Mn2+, Au3+, Ca2+, Ag+, Sr2+, and Ba2+), the vesicle phase generally precipitates. Metal salts with complex speciation (Al3+, Cu2+, Co2+, and Fe2+) added to the micellar phase drive the formation of wormlike gels, often observed for surfactants in water. On the contrary, free metal ions (Cr2+, Mn2+, Ca2+, and Ag+) added to the same micellar phase unexpectedly drive the formation of hydrogels with a fibrillar structure, generally observed for complex amphiphiles (peptides, peptide-derivatives) but not for surfactants. Oscillatory rheology shows that the elastic properties vary between a few tens of Pa up to 5 kPa for a given glucolipid concentration (3 wt %). This work hence shows the first example of preparing metallogels from biological surfactants

Energy Landscape of the Sugar Conformation Controls the Sol-to-Gel Transition in Self-Assembled Bola Glycolipid Hydrogels

Self-assembled fibrillar network hydrogels and organogels are commonly obtained through a crystallization process as fibers upon being induced by external stimuli such as temperature or pH. The gel-to-sol-to-gel transition is generally readily reversible, and the rate of change of the stimulus determines the fiber homogeneity and eventual elastic properties of the gels. However, recent work shows that in some specific cases, fibrillation occurs for a given molecular conformation and the sol-to-gel transition depends on the relative energetic stability of one conformation over the other and not on the rate of change of the stimuli. We observe such a phenomenon on a class of bolaform glycolipids, sophorosides, similar to the well-known sophorolipid biosurfactants but composed of two symmetric sophorose units. A combination of oscillatory rheology, small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy, and in situ rheology coupled with SAXS using synchrotron radiation shows that below 14 °C, twisted nanofibers are the thermodynamic phase. Between 14 and about 33 °C, nanofibers coexist with micelles and a strong hydrogel forms, the sol-to-gel transition being readily reversible in this temperature range. However, above the annealing temperature of about 40 °C, the micelle morphology becomes kinetically trapped for hours, even upon cooling, whichever the rate, to 4 °C. A combination of solution and solid-state nuclear magnetic resonance spectroscopy studies suggests two different conformations of the 1″, 1′, and 2′ carbon stereocenters of sophorose, precisely at the β­(1,2) glycosidic bond, for which several combinations of the dihedral angles are known to provide at least three energetic minima of comparable magnitude, with each corresponding to a given sophorose conformation

Stacking Interactions and Flexibility of Human Telomeric Multimers

G-quadruplexes (G4s) are helical four-stranded structures forming from guanine-rich nucleic acid sequences, which are thought to play a role in cancer development and malignant transformation. Most current studies focus on G4 monomers, yet under suitable and biologically relevant conditions, G4s undergo multimerization. Here, we investigate the stacking interactions and structural features of telomeric G4 multimers by means of a novel low-resolution structural approach that combines small-angle X-ray scattering (SAXS) with extremely coarse-grained (ECG) simulations. The degree of multimerization and the strength of the stacking interaction are quantitatively determined in G4 self-assembled multimers. We show that self-assembly induces a significant polydispersity of the G4 multimers with an exponential distribution of contour lengths, consistent with a step-growth polymerization. On increasing DNA concentration, the strength of the stacking interaction between G4 monomers increases, as well as the average number of units in the aggregates. We utilized the same approach to explore the conformational flexibility of a model single-stranded long telomeric sequence. Our findings indicate that its G4 units frequently adopt a beads-on-a-string configuration. We also observe that the interaction between G4 units can be significantly affected by complexation with benchmark ligands. The proposed methodology, which identifies the determinants that govern the formation and structural flexibility of G4 multimers, may be an affordable tool aiding in the selection and design of drugs that target G4s under physiological conditions

Continuous Thermal Collapse of the Intrinsically Disordered Protein Tau Is Driven by Its Entropic Flexible Domain

The tau protein belongs to the category of Intrinsically Disordered Proteins (IDP), which in their native state lack a folded structure and fluctuate between many conformations. In its physiological state, tau helps nucleating and stabilizing the microtubules’ (MTs) surfaces in the axons of the neurons. Tau is mainly composed by two domains: (i) the binding domain that tightly bounds the MT surfaces and (ii) the projection domain that exerts a long-range entropic repulsive force and thus provides the proper spacing between adjacent MTs. Tau is also involved in the genesis and in the development of the Alzheimer disease when it detaches from MT surfaces and aggregates in paired helical filaments. Unfortunately, the molecular mechanisms behind these phenomena are still unclear. Temperature variation, rarely considered in biological studies, is here used to provide structural information on tau correlated to its role as an entropic spacer between adjacent MTs surfaces. In this paper, by means of small-angle X-ray scattering and molecular dynamics simulation, we demonstrate that tau undergoes a counterintuitive collapse phenomenon with increasing temperature. A detailed analysis of our results, performed by the Ensemble Optimization Method, shows that the thermal collapse is coupled to the occurrence of a transient long-range contact between a region encompassing the end of the proline-rich domain P2 and the first part of the repeats domain, and the region of the N-terminal domain entailing residues 80–150. Interestingly these two regions involved in the tau temperature collapse belong to the flexible projection domain that acts as an entropic bristle and regulates the MTs’ architecture. Our results show that temperature is an important parameter that influences the dynamics of the tau projection domain, and hence its entropic behavior

Self-Assembly of Rhamnolipid Bioamphiphiles: Understanding the Structure–Property Relationship Using Small-Angle X‑ray Scattering

The structure–property relationship of rhamnolipids, RLs, well-known microbial bioamphiphiles (biosurfactants), is explored in detail by coupling cryogenic transmission electron microscopy (cryo-TEM) and both ex situ and in situ small-angle X-ray scattering (SAXS). The self-assembly of three RLs with reasoned variation of their molecular structure (RhaC10, RhaC10C10, and RhaRhaC10C10) and a rhamnose-free C10C10 fatty acid is studied in water as a function of pH. It is found that RhaC10 and RhaRhaC10C10 form micelles in a broad pH range and RhaC10C10 undergoes a micelle-to-vesicle transition from basic to acid pH occurring at pH 6.5. Modeling coupled to fitting SAXS data allows a good estimation of the hydrophobic core radius (or length), the hydrophilic shell thickness, the aggregation number, and the surface area per RL. The essentially micellar morphology found for RhaC10 and RhaRhaC10C10 and the micelle-to-vesicle transition found for RhaC10C10 are reasonably well explained by employing the packing parameter (PP) model, provided a good estimation of the surface area per RL. On the contrary, the PP model fails to explain the lamellar phase found for the protonated RhaRhaC10C10 at acidic pH. The lamellar phase can only be explained by values of the surface area per RL being counterintuitively small for a di-rhamnose group and folding of the C10C10 chain. These structural features are only possible for a change in the conformation of the di-rhamnose group between the alkaline and acidic pH