Supramolecular single-chain polymeric nanoparticles

Nature has unparalleled control over the conformation and dynamics of its folded macromolecular structures. Nature's ability to arrange amino acids into a precise spatial organization by way of folding allows proteins to fulfill specific functions in an extremely efficient manner. Chemists and materials scientists have used the delicate structure-function relationships observed in proteins to elucidate nature's design principles. These insights have led to the development of various revolutionary macromolecular architectures, mimicking the structural features of proteins. In this review, we focus on the folding of single polymer chains into well-defined nanoparticles using supramolecular interactions and their possible use as enzyme mimics

Effect of intra- versus intermolecular cross-linking on the supramolecular folding of a polymer chain

Anfinsen's famous experiment showed that the restoration of catalytic activity of a completely unfolded ribonuclease A is only possible when the correct order of events is followed during the refolding process. Inspired by this work, the effect of structural constraints induced by covalent cross-links on the folding of a synthetic polymer chain via hydrogen-bonding interactions is investigated. Hereto, methacrylate-based monomers comprising either benzene-1,3,5-tricarboxamide (BTA)-based or coumarin-based pendants are copolymerized with n-butyl methacrylate in various ratios via reversible addition-fragmentation chain-transfer (RAFT) polymerization. To assess whether the folding and single-chain polymeric nanoparticle (SCPN) formation depend on the order of events, we compare two folding pathways. In the one case, we first covalently cross-link the coumarin pendants within the polymers in a solvent that prevents hydrogen bonding, after which hydrogen bonding is activated, inducing folding of the polymer. In the other case, we induce hydrogen-bonding interactions between tethered BTAs prior to covalent cross-linking of the coumarin pendants. A combination of circular dichroism (CD) spectroscopy, UV-vis spectroscopy, size-exclusion chromatography (SEC), and dynamic light scattering (DLS) is employed to understand the effect of the structural constraints on the folding behavior of these synthetic polymers. The results show that like in ribonuclease A, the order of events matters greatly and determines the outcome. Importantly, a hydrogen-bond-promoting solvent prevents the formation of SCPNs upon covalent cross-linking and results in multichain aggregates. In contrast, covalently cross-linking the polymer when no hydrogen bonds are present followed by inducing hydrogen bonding favors the formation of SCPNs above the UCST of the methacrylate-based polymer. To our surprise, the two systems show a fundamentally different response to changes in temperature, indicating that also in synthetic polymers differences in the folding pathway induce differences in the properties of the resultant nanostructures

How Water in Aliphatic Solvents Directs the Interference of Chemical Reactivity in a Supramolecular System

Water is typically considered to be insoluble in alkanes. Recently, however, monomerically dissolved water in alkanes has been shown to dramatically impact the structure of hydrogen-bonded supramolecular polymers. Here, we report that water in methylcyclohexane (MCH) also determines the outcome of combining a Michael reaction with a porphyrin-based supramolecular system. In dry conditions, the components of the reaction do not affect or destabilize the supramolecular polymer, whereas in ambient or wet conditions the polymers are rapidly destabilized. Although spectroscopic investigations show no effect of water on the molecular structure of the supramolecular polymer, light scattering and atomic force microscopy experiments show that water increases the flexibility of the supramolecular polymer and decreases the polymer length. Through a series of titrations, we show that a cooperative interaction, involving the coordination of the amine catalyst to the porphyrin and complexation of the substrates to the flexible polymers invokes the depolymerization of the aggregates. Water crucially stabilizes these cooperative interactions to cause complete depolymerization in humid conditions. Additionally, we show that the humidity-controlled interference in the polymer stability occurs with various substrates, indicating that water may play a ubiquitous role in supramolecular polymerizations in oils. By controlling the amount of water, the influence of a covalent chemical process on noncovalent aggregates can be mediated, which holds great potential to forge a connection between chemical reactivity and supramolecular material structure. Moreover, our findings highlight that understanding cooperative interactions in multicomponent noncovalent systems is crucial to design complex molecular systems

Photodynamic control of the chain length in supramolecular polymers: switching an intercalator into a chain capper

Supramolecular systems are intrinsically dynamic and sensitive to changes in molecular structure and external conditions. Because of these unique properties, strategies to control polymer length, composition, comonomer sequence, and morphology have to be developed for sufficient control over supramolecular copolymerizations. We designed photoresponsive, mono acyl hydrazone functionalized benzene-1,3,5-tricarboxamide (m-BTA) monomers that play a dual role in the coassembly with achiral alkyl BTAs (a-BTA). In the E isomer form, the chiral m-BTA monomers intercalate into stacks of a-BTA and dictate the chirality of the helices. Photoisomerization to the Z isomer transforms the intercalator into a chain capper, allowing dynamic shortening of chain length in the supramolecular aggregates. We combine optical spectroscopy and light-scattering experiments with theoretical modeling to show the reversible decrease in length when switching from the E to Z isomer of m-BTA in the copolymer with inert a-BTA. With a mass-balance thermodynamic model, we gain additional insights into the composition of copolymers and length distributions of the species over a broad range of concentrations and mixing ratios of a-BTA/m-BTA. Moreover, the model was used to predict the impact of an additive (chain capper and intercalator) on the chain length over a range of concentrations, showing a remarkable amplification of efficiency at high concentrations. By employing a stimuli-responsive comonomer in a mostly inert polymer, we can cooperatively amplify the effect of the switching and obtain photocontrol of polymer length. Moreover, this dynamic decrease in chain length causes a macroscopic gel-to-sol phase transformation of the copolymer gel, although 99.4% of the organogel is inert to the light stimulus

Tuning the length of cooperative supramolecular polymers under thermodynamic control

In the field of supramolecular (co)polymerizations, the ability to predict and control the composition and length of the supramolecular (co)polymers is a topic of great interest. In this work, we elucidate the mechanism that controls the polymer length in a two-component cooperative supramolecular polymerization and unveil the role of the second component in the system. We focus on the supramolecular copolymerization between two derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers: a-BTA and Nle-BTA. As a single component, a-BTA cooperatively polymerizes into long supramolecular polymers, whereas Nle-BTA only forms dimers. By mixing a-BTA and Nle-BTA in different ratios, two-component systems are obtained, which are analyzed in-depth by combining spectroscopy and light-scattering techniques with theoretical modeling. The results show that the length of the supramolecular polymers formed by a-BTA is controlled by competitive sequestration of a-BTA monomers by Nle-BTA, while the obvious alternative Nle-BTA acts as a chain-capper is not operative. This sequestration of a-BTA leads to short, stable species coexisting with long cooperative aggregates. The analysis of the experimental data by theoretical modeling elucidates the thermodynamic parameters of the copolymerization, the distributions of the various species, and the composition and length of the supramolecular polymers at various mixing ratios of a-BTA and Nle-BTA. Moreover, the model was used to generalize our results and to predict the impact of adding a chain-capper or a competitor on the length of the cooperative supramolecular polymers under thermodynamic control. Overall, this work unveils comprehensive guidelines to master the nature of supramolecular (co)polymers and brings the field one step closer to applications

Self-Assembled Multi- and Single-Chain Glyconanoparticles and Their Lectin Recognition

In this work, we describe the physicochemical characterization of amphiphilic glycopolymers synthesized via copper(0)-mediated reversible-deactivation radical polymerization (Cu-RDRP). Depending on the chemical composition of the polymer, these glycopolymers are able to form multi-chain or single-chain polymeric nanoparticles. The folding of these polymers is first of all driven by the amphiphilicity of the glycopolymers and furthermore by the supramolecular formation of helical supramolecular stacks of benzene-1,3,5-tricarboxamides (BTAs) stabilized by threefold hydrogen bonding. The obtained polymeric nanoparticles were subsequently evaluated for their lectin-binding affinity toward a series of mannose- and galactose-binding lectins via surface plasmon resonance. We found that addition of 2-ethylhexyl acrylate to the polymer composition results in compact particles, which translates to a reduction in binding affinity, whereas with the addition of BTAs, the relation between the nature of the particle and the binding ability system becomes more unpredictable

The effect of dendritic pendants on the folding of amphiphilic copolymers via supramolecular interactions

The supramolecular folding of amphiphilic heterograft copolymers equipped with dendritic pendants is investigated using a combination of proton nuclear magnetic resonance (1H NMR) spectroscopy, small-angle X-ray scattering, and circular dichroism spectroscopy. Hereto, the linear poly(ethylene glycol) pendants normally used to convey water compatibility are partially substituted with branched analogues. For one set of copolymers, second-generation polyglycerol dendrons are directly attached to the polymer backbone, while for the other a hydrophilic linker is placed in between. The results show that the branching of the hydrophilic pendants affects the local structure of the folded copolymer but does not influence the overall conformation and single-chain character of the folded copolymers in solution. All copolymers fold into 4–5 nm single-chain polymeric nanoparticles with a very compact spherical morphology, independent of the dendritic content of the copolymer. Intriguingly, the incorporation of the dendritic pendants affects the formation of a structured interior even at low incorporation ratios

Mimicking active biopolymer networks with a synthetic hydrogel

\u3cp\u3eStiffening due to internal stress generation is of paramount importance in living systems and is the foundation for many biomechanical processes. For example, cells stiffen their surrounding matrix by pulling on collagen and fibrin fibers. At the subcellular level, molecular motors prompt fluidization and actively stiffen the cytoskeleton by sliding polar actin filaments in opposite directions. Here, we demonstrate that chemical cross-linking of a fibrous matrix of synthetic semiflexible polymers with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) produces internal stress by induction of a coil-to-globule transition upon crossing the lower critical solution temperature of PNIPAM, resulting in a macroscopic stiffening response that spans more than 3 orders of magnitude in modulus. The forces generated through collapsing PNIPAM are sufficient to drive a fluid material into a stiff gel within a few seconds. Moreover, rigidified networks dramatically stiffen in response to applied shear stress featuring power law rheology with exponents that match those of reconstituted collagen and actomyosin networks prestressed by molecular motors. This concept holds potential for the rational design of synthetic materials that are fluid at room temperature and rapidly rigidify at body temperature to form hydrogels mechanically and structurally akin to cells and tissues.\u3c/p\u3

Relationships between PLP, glucose and CABs.

<p>(A) Glucose concentration in the hemolymph of wild type (wt) and <i>dPdxk</i> mutant larvae. Columns are the means of 8 independent samples of 10 larvae ±SE; *, glucose content is significantly higher than in wild type with p<0.001 in the Student t test. (B) CAB frequencies and relative intracellular glucose (G) concentration in wild type (wt) and <i>dPdxk</i> mutant brains incubated in saline/FBS with the indicated G contents (protocol 2; <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004199#pgen-1004199-g001" target="_blank">figure 1</a>). §, includes cells with >5 CABs. * and †, significantly different in the Student t test with p<0.001 and p<0.05, respectively.</p