Ionic Liquids Containing Block Copolymer Based Supramolecules

Block copolymer (BCP)-based supramolecules provide a versatile strategy to generate functional materials using noncovalent bond between small molecules and BCPs. Here, we report supramolecules composed of phenol-containing ionic liquids (ILs) hydrogen bonded to BCP, polystyrene-<i>block</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP). IL-containing supramolecules exhibit ordered structures in a wide range of IL loading and chemistry. Rheological behaviors and nanostructures of IL-containing supramolecules can be tuned by controlling the IL loading without losing ordered structure. The hydrogen bonds and nanostructures can be retained in a wide range of temperatures with different IL chemistry. Supramolecules provide a diverse platform toward IL materials with ordered structure and tunable properties with high tolerance of thermal treatment and processing

Nanoparticle Assemblies in Supramolecular Nanocomposite Thin Films: Concentration Dependence

The phase behavior of supramolecular nanocomposite thin films was systematically investigated as a function of nanoparticle (NP) loading from 1 to >50 wt %. The coassembly of NP and supramolecule can be divided into five regimes, from a supramolecule-guided assembly to a NP governing assembly process, depending on the energetic contributions from the surface energy, NP-supramolecule interaction, and the kinetic pathway of the assembly process. A range of morphologies such as 1D NP chains, 2D sheets, 3D NP assemblies, and NP solids can be readily obtained, providing opportunities to meet structural control in nanocomposites for a wide range of applications

A Small-Angle X‑ray Scattering Study of α‑helical Bundle-Forming Peptide–Polymer Conjugates in Solution: Chain Conformations

As a new family of soft materials, peptide/protein–polymer conjugates can lead to a wide range of potential biological and nonbiological applications. The performance of these materials depends on the protein structure and phase behavior arising from a balance between the enthalpic interactions of the components and surrounding media as well as the entropic contribution associated with polymer chain deformation. There is a great need to perform structural studies in solution that systematically investigate the polymer chain conformation upon linkage to a peptide or protein so as to evaluate how polymers affect the protein structure of the biomolecule and, consequently, its functionality. Combinations of a range of factors including low contrast, weak scattering signals in dilute solutions as well as difficulties in separating the component scattering contributions, pose significant challenges to structural characterization. Here we present a synchrotron small-angle X-ray scattering (SAXS) study of two model helix bundle forming peptide–polymer conjugates and show that with analytical modeling of the scattering intensity detailed structural information on both peptide structure and polymer conformation can be extracted. The peptide–poly­(ethylene glycol) (PEG) conjugates are based on peptides that self-associate to form well-defined 3- or 4-helix bundles and the PEG chain is covalently linked either to the end or the side of the peptide (i.e. end- or side-conjugation). Using a simplified analytical geometrical body form factor model, where the peptide–polymer bundles are modeled as parallel cylinders with attached Gaussian chains, a quantitative description of the scattering behavior can be reached. On the basis of the simplified structural model, the protein tertiary structures, i.e., the α-helix bundle, remains largely intact and maintains its oligomeric state but exhibits slight swelling in solution with respect to the crystal structure. The PEG chain conformation appears to slightly depend on the conjugate architecture. In terms of the chain dimension represented by <i>R</i>_<i>g</i>, the end-conjugated PEG exhibit similar value as compared to free PEG for the molecular weight studied (2 kDa). For the side-conjugates our simple scattering model seems to indicate a systematically slightly lower values for <i>R</i>_<i>g</i>, i.e., a slight compression, in particular for the highest molecular weight (5 kDa). However, considering the limitations of the model and experimental uncertainties, further investigations, such as neutron scattering, is needed to illustrate detailed chain conformation. The present studies can be extended to other peptide–polymer or protein–polymer hybrid systems to extract information on both protein structure and polymer chain conformation. This work will thus provide valuable guidance to understand their structure and phase behavior using X-ray and neutron scattering

Micelle Stabilization via Entropic Repulsion: Balance of Force Directionality and Geometric Packing of Subunit

Nanoparticles, 10–30 nm in size, have shown great prospects as nanocarriers for drug delivery. We designed amphiphiles based on 3-helix peptide-PEG conjugate forming 15 nm micelles (defined as “3-helix micelles”) with good in vivo stability. Here, we investigated the effect of the site of PEG conjugation on the kinetic stability and showed that the conjugation site affects the PEG chain conformation and the overall molecular architecture of the subunit. Compared to the original design where the PEG chain is located in the middle of the 3-helix bundle, micelle kinetic stability was reduced when the PEG chain was attached near the N-terminus (<i>t</i>_1/2 = 35 h) but was enhanced when the PEG chain was attached near the C-terminus (<i>t</i>_1/2 = 80 h). Quantitative structural and kinetic analysis suggest that the kinetic stability was largely dictated by the combined effects of entropic repulsion associated with PEG chain conformation and the geometric packing of the trimeric subunits. The modular design approach coupled with a variety of well-defined protein stucture and functional polymers will significantly expand the utility of these materials as nanocarriers to meet current demands in nanomedine

Nanorod-Based Supramolecular Nanocomposites: Effects of Nanorod Length

Nanorods (NRs) have unique anisotropic properties that are desirable for various applications. Block copolymer-based supramolecules present unique opportunities to control inter-rod ordering and macroscopic alignment of NRs to fully take advantage of their unique anisotropic properties. Here, we studied the effects of NR aspect ratio where the NR length is in the range of 20–180 nm on the assemblies of NRs in supramolecular framework. At a moderate loading (∼3 vol %), well-ordered assemblies of 37–90 nm NRs embedded in the supramolecular framework were formed. Shorter NRs (∼22 nm) coassemble with the supramolecule but were not well-ordered and displayed little orientational control within the microdomains. In contrast, longer NRs (∼180 nm) formed kinetically trapped states that restricted the formation of well-ordered coassemblies in NR/supramolecule blends. Additionally, the NRs are shown to be capable of kinetically trapping the system after normally reversible morphological transitions triggered by the thermal dissociation of the supramolecule, arresting the system away from a stable morphology. These studies shed light on the effects of NR-induced kinetic arrest on the self-assembly of a supramolecular nanocomposite

Poly(ethylene glycol) Conjugation Stabilizes the Secondary Structure of α‑Helices by Reducing Peptide Solvent Accessible Surface Area

We investigate the effect of poly­(ethylene glycol) (PEG) side-chain conjugation on the conformational behavior of an α-helix using molecular dynamics simulations in explicit solvents of varying hydrophobicity. Our simulations illustrate an increase in peptide helicity with increasing PEG molecular weight in the range ∼400 to 1800 Da. The data with varying PEG contour lengths as well as constant force pulling simulations that allow control over the end-to-end length of PEG indicate a strong inverse correlation between peptide helicity and solvent accessible surface area (SASA). A residue-based mapping analysis reveals that the formation of a protecting PEG shell around peptide helix in water is facilitated by two distinct mechanisms that depend on the solvent environment. First, cationic residues such as lysine interact favorably with PEG due to strong polar interactions with PEG oxygen atoms. Additionally, we find that hydrophobic residues interact strongly with PEG to reduce their SASA in polar solvents by polymer shielding. Our simulations illustrate that these two mechanisms that involve side-chain chemistry and solvent polarity govern the preferred conformation of PEG on the helix surface and thus the stability of peptide secondary structure. These findings elucidate the molecular mechanisms underpinning recent experimental findings on the stability and conformational dynamics of protein–PEG conjugates

Achieving 3‑D Nanoparticle Assembly in Nanocomposite Thin Films via Kinetic Control

Nanocomposite thin films containing well-ordered nanoparticle (NP) assemblies are ideal candidates for the fabrication of metamaterials. Achieving 3-D assembly of NPs in nanocomposite thin films is thermodynamically challenging as the particle size gets similar to that of a single polymer chain. The entropic penalties of polymeric matrix upon NP incorporation leads to NP aggregation on the film surface or within the defects in the film. Controlling the kinetic pathways of assembly process provides an alternative path forward by arresting the system in nonequilibrium states. Here, we report the thin film 3-D hierarchical assembly of 20 nm NPs in supramolecules with a 30 nm periodicity. By mediating the NP diffusion kinetics in the supramolecular matrix, surface aggregation of NPs was suppressed and NPs coassemble with supramolecules to form new 3-D morphologies in thin films. The present studies opened a viable route to achieve designer functional composite thin films via kinetic control

Thermally Controlled Morphologies in a Block Copolymer Supramolecule via Nonreversible Order–Order Transitions

Block copolymer (BCP)-based supramolecules represent a versatile platform to generate functional nanostructures without the need for complex synthesis. The noncovalent bonding between the BCP and small molecules further opens opportunities to access thermal responsive assemblies. A BCP supramolecule containing cholesteric liquid crystal (LC) small molecules is observed to undergo thermally induced, nonreversible order–order transitions (OOTs), resulting in several well-defined morphologies readily tunable by annealing temperature. The nonreversible OOTs highlight the importance of small molecule phase transitions and intermolecular interactions on the overall phase behavior of the supramolecule. The present system also provides a route to manipulate local nanostructures via heating

Solution Structural Characterization of Coiled-Coil Peptide–Polymer Side-Conjugates

Detailed structural characterization of protein–polymer conjugates and understanding of the interactions between covalently attached polymers and biomolecules will build a foundation to design and synthesize hybrid biomaterials. Conjugates based on simple protein structures are ideal model system to achieve these ends. Here we present a systematic structural study of coiled-coil peptide–poly­(ethylene glycol) (PEG) side-conjugates in solution, using circular dichroism, dynamic light scattering, and small-angle X-ray scattering, to determine the conformation of conjugated PEG chains. The overall size and shape of side-conjugates were determined using a cylindrical form factor model. Detailed structural information of the covalently attached PEG chains was extracted using a newly developed model where each peptide–PEG conjugate was modeled as a Gaussian chain attached to a cylinder, which was further arranged in a bundle-like configuration of three or four cylinders. The peptide–polymer side-conjugates were found to retain helix bundle structure, with the polymers slightly compressed in comparison with the conformation of free polymers in solution. Such detailed structural characterization of the peptide–polymer conjugates, which elucidates the conformation of conjugated PEG around the peptide and assesses the effect of PEG on peptide structure, will contribute to the rational design of this new family of soft materials

Effect sizes and confidence intervals for each study in the meta-analysis involving unaffected relatives and healthy controls.

<p>Effect sizes and confidence intervals for each study in the meta-analysis involving unaffected relatives and healthy controls.</p