Assembly of Building Blocks by Double-End-Anchored Polymers in the Dilute Regime Mediated by Hydrophobic Interactions at Controlled Distances

Abstract

Hierarchical assembly of building blocks via competing, orthogonal interactions is a hallmark of many of nature's composite materials that do not require highly specific ligand−receptor interactions. To mimic this assembly mechanism requires the development of building blocks capable of tunable interactions. In the present work, we explored the interplay between repulsive (steric and electrostatic) and attractive hydrophobic forces. The designed building blocks allow hydrophobic forces to effectively act at controlled, large distances, to create and tune the assembly of membrane-based building blocks under dilute conditions, and to affect their interactions with cellular membranes via physical cross-bridges. Specifically, we employed double-end-anchored poly(ethylene glycol)s (DEA-PEGs)hydrophilic PEG tethers with hydrophobic tails on both ends. Using differential-interference-contrast optical microscopy, synchrotron small-angle Xray scattering (SAXS), and cryogenic electron microscopy, we investigated the ability of DEA-PEGs to mediate assembly in the dilute regime on multiple length scales and on practical time scales. The PEG length, anchor hydrophobicity, and molar fraction of DEA-PEG molecules within a membrane strongly affect the assembly properties. Additional tuning of the intermembrane interactions can be achieved by adding repulsive interactions via PEG-lipids (steric) or cationic lipids to the DEA-PEG-mediated attractions. While the optical and electron microscopy imaging methods provided qualitative evidence of the ability of DEA-PEGs to assemble liposomes, the SAXS measurements and quantitative line-shape analysis in dilute preparations demonstrated that the ensemble average of loosely organized liposomal assemblies maintains DEA-PEG concentration-dependent tethering on defined nanometer length scales. For cationic liposome−DNA nanoparticles (CL−DNA NPs), aggregation induced by DEA-PEGs decreased internalization of NPs by cells, but tuning the DEA-PEG-induced attractions by adding repulsive steric interactions via PEG-lipids limited aggregation and increased NP uptake. Furthermore, confocal microscopy imaging together with colocalization studies with Rab11 and LysoTracker as markers of intracellular pathways showed that modifying CL−DNA NPs with DEA-PEGs alters their interactions with the plasma and endosomal membranes.

Aging-Induced Structural Transition of Nanoscale Oleanolic Acid Amphiphiles and Selectivity against Gram-Positive Bacteria

“…It should be emphasized that, while a progressive breaking of intermolecular hydrogen bonds occurs upon increasing the temperature, an increase in the hydrophobic effect is usually expected. The hydrophobic effect plays an important role in the structural transition . This finding is in good agreement with our previous study on their gelation properties …”

“…The hydrophobic effect plays an important role in the structural transition. 14 This finding is in good agreement with our previous study on their gelation properties. 24 Vibrational Circular Dichroism Spectroscopy.…”

“…In recent years, the focus has been shifted toward kinetically trapped assemblies and out-of-equilibrium systems . Kinetically trapped structures are unstable, and they can be potentially transformed into thermodynamically stable structures, either with time (i.e., aging-induced transition) or by supplying adequate activation energy and/or by change of pH, solvent, temperature, and additives . Tuning the physicochemical properties of self-assembled structures offers practical applicability such as enhanced solubilization and encapsulation of drugs that are poorly soluble in water, delivery vehicles, and confined catalysis relying upon the morphological features of the self-assembled structures …”

Nano-assembly of cytotoxic amides of moronic and morolic acid

“…NMR measurements were performed either on a Bruker AVANCE 500 MHz or on a Bruker AVANCE II 600 MHz spectrometer equipped with a 5 mm TCI cryoprobe in a 5 mm tube in different solvents. The 1 H NMR and the 13 C NMR spectra were recorded at 600.13 MHz and 150.90 MHz (AVANCE II 600 MHz) in CDCl 3 or CD 3 OD using tetramethylsilane (d = 0.0 -CDCl 3 ) or signal of the solvent (d = 3.31 or 49.50 for 1 H/ 13 C -CD 3 OD) as internal references. 1 H NMR data are presented in the following order: chemical shift (d) expressed in ppm, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet), number of protons, and coupling constants in Hertz.…”

“…7 In recent years, the focus has been shifted towards kinetically trapped assemblies, 8 and out-of-equilibrium systems. 9 Kinetically trapped structures are unstable, and they can be potentially transformed into thermodynamically stable structures, 10 either with time (aging-induced transition) 11 or by supplying adequate activation energy by changing the pH, 12 solvent, 8 temperature, 13 or additives. 14 Adjusting the physicochemical characteristics of self-assembled structures enables practical applicability, e.g., enhanced solubilization and encapsulation of drugs poorly soluble in water, delivery vehicles and confined catalysis relying upon the morphological characteristics of the self-assembled structures.…”