Self-assembled Tubules Research Articles

Stimuli-Sensitive Self-Assembled Tubules Based on Lysine-Derived Surfactants for Delivery of Antimicrobial Proteins.

Drug delivery vectors based on amphiphiles have important features such as versatile physicochemical properties and stimuli-responsiveness. Amino acid-based surfactants are especially promising amphiphiles due to their enhanced biocompatibility compared to conventional surfactants. They can self-organize into micelles, vesicles and complex hierarchical structures, such as fibers, twisted and coiled ribbons, and tubules. In this work, we investigated the self-assembly and drug loading properties of a family of novel anionic double-tailed lysine-derived surfactants, with variable degree of tail length mismatch, designated as mLys10 and 10Lysn, where m and n are the number of carbon atoms in the tails. These surfactants form tubular aggregates with assorted morphologies in water that undergo gelation due to dense entanglement, as evidenced by light and electron microscopy. Lysozyme (LZM), an enzyme with antimicrobial properties, was selected as model protein for loading. After the characterization of the interfacial properties and phase behavior of the amphiphiles, the LZM-loading ability of the tubules was investigated, under varying experimental conditions, to assess the efficiency of the aggregates as pH- and temperature-sensitive nanocarriers. Further, the toxicological profile of the surfactants per se and surfactant/LZM hydrogels was obtained, using human skin fibroblasts (BJ-5ta cell line). Overall, the results show that the tubule-based hydrogels exhibit very interesting properties for the transport and controlled release of molecules of therapeutic interest.

Charge Regulation of Self-Assembled Tubules by Protonation for Efficiently Selective and Controlled Drug Delivery.

SummaryDespite the success for targeted delivery in the body, the efficient release without side effects caused by residual drug remains a challenge. For reducing residual drug, the pH-responsive carriers were prepared by self-assembly from aromatic macrocycles, which were non-toxic and biocompatible. The inner surroundings of aromatic macrocycles could be protonated positively by acid inducing the separation of neighboring macrocycles. Thus, Dox-loaded carriers successfully inhibited the proliferation of carcinoma cells (HepG2 and 4T1) rather than normal cells (HL7702). The effects were further proved in vivo without systemic cytotoxicity. Notably, the responsive environment for drug release depended on the concentration of carriers. Particularly, drug release was promoted by carrier separation. Carrier 2 exhibited preferable anticancer efficacy than carrier 1 due to the efficient release of Dox by full separation of the carrier. Collectively, we have developed a novel strategy serving as a selective and controlled drug release platform for cancer therapeutics.

Effect of water on self-assembled tubules in β-sitosterol + γ-oryzanol-based organogels

Mixtures of β-sitosterol and γ-oryzanol form a network in triglyceride oil that may serve as an alternative to the network of small crystallites of triglycerides occurring in regular oil structuring. The present x-ray diffraction study investigates the relation between the crystal forms of the individual compounds and the mixture in oil, water and emulsion. β-Sitosterol and γ-oryzanol form normal crystals in oil, in water, or in emulsions. The crystals are sensitive to the presence of water. The mixture of β-sitosterol + γ-oryzanol forms crystals in water and emulsions that can be traced back to the crystals of the pure compounds. Only in oil, a completely different structure emerges in the mixture of β-sitosterol + γ-oryzanol, which bears no relation to the structures that are formed by both individual compounds, and which can be identified as a self-assembled tubule (diameter 7.2±0.1 nm, wall thickness 0.8±0.2 nm).

Structuring in β-sitosterol + γ-oryzanol-based emulsion gels during various stages of a temperature cycle

Water-in-oil emulsions were prepared, structured only by a mixture of sitosterol and oryzanol and without further emulsifiers, containing 16 and 32% total sterol(esters)s on lipid phase and 10, 30 or 60% water. Previously, mixtures of β-sitosterol + γ-oryzanol were shown to form self-assembled tubules in triglyceride oil with diameter 7.2 ± 0.1 nm and a wall thickness 0.8 ± 0.2 nm. At 16% total sterol concentration, the SAXS diffraction patterns only demonstrate the presence of sitosterol and oryzanol crystals, but not of tubules. At 32% total sterol concentration, the diffraction patterns reveal the presence of tubules next to the crystals of the individual compounds. However, the tubule structure in these emulsions was more complicated than in pure oil and changed during storage, revealing the formation of bigger structures in the emulsion over time. In the cooling stage of a temperature cycle, water droplets nucleate at the tip of the fibres that reappear as a consequence of crystallisation.

Impregnation of Tubular Self-Assemblies into Dextran Hydrogels

Amine groups are the building units of proteins. The incorporation of amine groups into polyethylene glycol diacrylate (PEGDA) hydrogel through dextran-allyl isocyanate-ethylamine (Dex-AE) enhances sustained protein release by introducing effective interactions. To investigate such an interaction effect and to improve protein release, we impregnated self-assembled tubular structures from dextran-bromoethylamine (Dex-BH) and dextran-chloroacetic acid (Dex-CA) into Dex-AE/PEGDA hydrogel. The morphology data obtained from scanning electron microscopy (SEM) reveal that pure PEGDA hydrogel had no effect on the distribution of the self-assembled tubules; the introduction of Dex-AE brought about the dispersion of these tubules, and an increase in Dex-AE content led to more evenly distributed structures. Moreover, the implantation of the self-assembled tubules had no distinct effect on the swelling capacity of the hybrid self-assembly embedded hydrogels. The in vitro albumin release study was carried out in a pH 7.4 buffer solution; the results show that the implantation of the self-assembly into the hydrogels reduced the burst release and prolonged the protein release time. These findings demonstrate that the impregnation of tubular self-assembly into hydrogel makes the hybrid hydrogel an excellent protein delivery system.

Positioning and Alignment of Lipid Tubules on Patterned Au Substrates

This paper presents a method for positioning and aligning self-assembled tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphochloline (DC(8,9)PC) by withdrawing a patterned Au substrate from tubule solution. The patterned Au substrates with alternating bare Au stripes and thiol monolayer stripes are formed by microcontact printing. We find that the lipid tubules selectively adsorb on the bare Au stripes but show no orientation order. By withdrawing the patterned Au substrates at the direction along the stripes from tubule solution, the lipid tubules are found to be aligned along the direction of the Au stripes. The angular distribution and the density of the aligned lipid tubules depend on the withdrawal rates and the adsorption time, respectively. We conclude that forces causing tubule alignment that originate in the surface tension associated with the moving meniscus dominate alignment forces exerted by the patterned Au substrates.

Self-Assembled Lipid Tubules: Synthesis, Characterization, and Ordered Arrays

AbstractThe rolling of lipid bilayer sheets into hollow cylindrical tubules have emerged as a group of interesting supramolecular nanostructures. Here, we image the self-assembled tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphochloline (DC8,9PC) with atomic force microscopy. Nanoscale ripple structures with a periodicity of ~ 200nm in the cylindrical lipid tubules are observed. We develop two simple methods based on microfluidic networks and surface patterning to produce two dimensional ordered arrays of parallel aligned lipid tubules on substrates.

This Week in PNAS

Imaging of self-assembled phospholipid tubules Tilt ordering of chiral phospholipids in self-assembled tubules has been imaged with a liquid-crystal optical amplification system, Yue Zhao et al. report. The authors found that the tubules can have both uniform and modulated tilt states. Chiral

Theory of Self-Assembled Tubules and Helical Ribbons

Many types of amphiphilic molecules self-assemble in solution to form cylindrical tubules and helical ribbons. Some examples include diacetylenic lipids, amide amphiphiles, bile, and diblock copolymers. Researchers have proposed a variety of models to explain the formation of these high-curvature structures. These models can be divided into two broad categories: models based on the chiral elastic properties of membranes, and models based on other effects, including electrostatic interactions, elasticity of orientational order, and spontaneous curvature. In this paper, we review the range of theoretical approaches and compare them with relevant experiments. We argue that the category of models based on chiral elastic properties provides the most likely explanation of current experimental results, and we propose further theoretical and experimental research to give a more detailed test of these models.

Diacetylenic Lipid Tubules: Experimental Evidence for a Chiral Molecular Architecture

Molecular self-assembly is of key importance for the rational design of advanced materials. To investigate the causal relation between molecular structure and the consequent self-assembled microstructure, self-assembled tubules of diacetylenic lipids were studied. Circular-dichroism studies give experimental evidence that the formation of tubules is driven by chiral molecular packing, in agreement with recent theories of tubules. On the basis of these results, a molecular mechanism for the formation of tubules is proposed.