Supramolecular Nanofibers Research Articles

Functionalization of self-assembling peptide materials using molecular recognition of supramolecular peptide nanofibers

We recently developed a self-assembling peptide, E1Y9 (Ac-E-YEYKYEYKY-NH2), that forms supramolecular nanofibers with hydrogelation properties in response to Ca2+ ions. In this study, we proposed a new method to functionalize supramolecular peptide nanofibers using fiber-binding peptides screened from a phage peptide library. Three fiber-binding peptides, namely, p1, p2, and p3, were successfully identified. The RGDS-conjugated forms of these peptides, namely, p1-RGDS, p2-RGDS, and p3-RGDS, significantly enhanced the adhesion of 3T3-L1 cells on E1Y9 nanofibers through noncovalent modification of E1Y9 nanofibers. This noncovalent modification using fiber-binding peptides was also effective for functionalization of E1Y9 hydrogels, as E1Y9 hydrogels modified with p1-RGDS or p2-RGDS promoted the proliferation of 3T3-L1 cells, compared with the E1Y9 hydrogel alone. Since p1 and p2 could bind to different sites on E1Y9 nanofibers, the additional enhancement in cell proliferation on E1Y9 hydrogels was achieved using both p1-RGDS and p2-RGDS. Thus, the functionalization of supramolecular peptide nanofibers using molecular recognition peptides will be a powerful tool for the development of functional materials. We proposed a new method to functionalize supramolecular peptide nanofibers using fiber-binding peptides screened from a phage peptide library. The RGDS-conjugated fiber-binding peptides significantly enhanced the adhesion of 3T3-L1 cells on E1Y9 nanofibers through noncovalent modification of E1Y9 nanofibers. This noncovalent modification using fiber-binding peptides was also effective for functionalization of E1Y9 hydrogels as cell culture materials that promoted the proliferation of 3T3-L1 cells. The functionalization of supramolecular peptide nanofibers using molecular recognition peptides will be a powerful tool for the development of functional materials.

Enhancing Long-Range Energy Transport in Supramolecular Architectures by Tailoring Coherence Properties.

Efficient long-range energy transport along supramolecular architectures of functional organic molecules is a key step in nature for converting sunlight into a useful form of energy. Understanding and manipulating these transport processes on a molecular and supramolecular scale is a long-standing goal. However, the realization of a well-defined system that allows for tuning morphology and electronic properties as well as for resolution of transport in space and time is challenging. Here we show how the excited-state energy landscape and thus the coherence characteristics of electronic excitations can be modified by the hierarchical level of H-type supramolecular architectures. We visualize, at room temperature, long-range incoherent transport of delocalized singlet excitons on pico- to nanosecond time scales in single supramolecular nanofibers and bundles of nanofibers. Increasing the degree of coherence, i.e., exciton delocalization, via supramolecular architectures enhances exciton diffusivities up to 1 order of magnitude. In particular, we find that single supramolecular nanofibers exhibit the highest diffusivities reported for H-aggregates so far.

Dynamic Detection of Active Enzyme Instructed Supramolecular Assemblies In Situ via Super-Resolution Microscopy.

Inspired by the self-assembly phenomena in nature, the instructed self-assembly of exogenous small molecules in a biological environment has become a prevalent process to control cell fate. Despite mounting examples of versatile bioactivities, the underlying mechanism remains less understood, which is in large hindered by the difficulties in the identification of those dynamic assemblies in situ. Here, with direct stochastic optical reconstruction microscopy, we are able to elucidate the dynamic morphology transformation of the enzyme-instructed supramolecular assemblies in situ inside cancer cells with a resolution below 50 nm. It indicates that the assembling molecules endure drastically different pathways between cell lines with different phosphatase activities and distribution. In HeLa cells, the direct formation of intracellular supramolecular nanofibers showed slight cytotoxicity, which was due to the possible cellular secretory pathway to excrete those exogenous molecules assemblies. In contrast, in Saos-2 cells with active phosphatase on the cell surface, assemblies with granular morphology first formed on the cell membranes, followed by a transformation into nanofibers and accumulation in cells, which induced Saos-2 cell death eventually. Overall, we provided a convenient method to reveal the in situ dynamic nanomorphology transformation of the supramolecular assemblies in a biological environment, in order to decipher their diverse biological activities.

Enabling sublingual peptide immunization with molecular self-assemblies

Short peptides are poorly immunogenic when delivered sublingually – under the tongue. Nanomaterial delivery of peptides could be utilized to improve immunogenicity towards designed sublingual vaccines, but nanomaterials have not been widely successful in sublingual vaccines owing to the challenges of transport through the sublingual mucosa. Here, we report that the sublingual immunogenicity of peptides is negligible, even in the presence of sublingual adjuvants or when PEGylated, but can be dramatically enhanced by assembly into supramolecular polymer-peptide nanofibers bearing low-molecular weight PEG, optimally between 2000 and 3000 Da. Neither PEGylation nor a sublingual adjuvant were capable of rendering peptides immunogenic without assembly into nanofibers. We found that PEG decreased nanofiber interactions with mucin and promoted longer residence time at the sublingual immunization site. Parallel investigations with shortened nanofibers indicated that the size of the assemblies had a surprisingly negligible influence over sublingual immunogenicity. In mice, optimized formulations were capable of raising strong and highly durable systemic antibody responses, antibodies in the upper respiratory and reproductive tracts, and systemic antigen-specific T-cell responses. These nanofiber-based sublingual vaccines were effective with both protein and nucleotide adjuvants and raised responses against both a model peptide epitope and a peptide epitope from M. tuberculosis. Further, PASylation (modification of nanofibers with peptide sequences rich in Pro, Ala, and Ser) could be substituted for PEGylation to also achieve sublingual immunogenicity. These findings indicated that surface properties supersede nanomaterial size in modulating sublingual nanomaterial immunogenicity, having important implications for the design of synthetic sublingual vaccines.

Highly Efficient and Tunable Filtering of Electrons' Spin by Supramolecular Chirality of Nanofiber-Based Materials.

Organic semiconductors and organic-inorganic hybrids are promising materials for spintronic-based memory devices. Recently, an alternative route to organic spintronic based on chiral-induced spin selectivity (CISS) is suggested. In the CISS effect, the chirality of the molecular system itself acts as a spin filter, thus avoiding the use of magnets for spin injection. Here, spin filtering in excess of 85% in helical π-conjugated materials based on supramolecular nanofibers at room temperature is reported. The high spin-filtering efficiency can even be observed in nanofibers assembled from mixtures of chiral and achiral molecules through chiral amplification effect. Furthermore and most excitingly, it is shown that both "up" and "down" orientations of filtered spins can be obtained in a single enantiopure system via the temperature-dependent helicity (P and M) inversion of supramolecular nanofibers. The findings showcase that materials based on helical noncovalently assembled systems are modular platforms with an emerging structure-property relationship for spintronic applications.

Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers.

The discovery of cell penetrating peptides (CPPs) with unique membrane activity has inspired the design and synthesis of a variety of cell penetrating macromolecules, which offer tremendous opportunity and promise for intracellular delivery of a variety of imaging probes and therapeutics. While cell penetrating macromolecules can be designed and synthesized to have equivalent or even superior cell penetrating activity compared with natural CPPs, most of them suffer from moderate to severe cytotoxicity. Inspired by recent advances in peptide self-assembly and cell penetrating macromolecules, in this work, we demonstrated a new class of peptide assemblies with intrinsic cell penetrating activity and excellent cytocompatibility. Supramolecular assemblies were formed through the self-assembly of de novo designed multidomain peptides (MDPs) with a general sequence of Kx(QW)6Ey in which the numbers of lysine and glutamic acid can be varied to control supramolecular assembly, morphology and cell penetrating activity. Both supramolecular spherical particles and nanofibers exhibit much higher cell penetrating activity than monomeric MDPs while supramolecular nanofibers were found to further enhance the cell penetrating activity of MDPs. In vitro cell uptake results suggested that the supramolecular cell penetrating nanofibers undergo macropinocytosis-mediated internalization and they are capable of escaping from the lysosome to reach the cytoplasm, which highlights their great potential as highly effective intracellular therapeutic delivery vehicles and imaging probes.

Protonation-induced self-assembly of bis-phenanthroline macrocycles into nanofibers arrayed with tetrachloroaurate, hexachloroplatinate or phosphomolybdate ions.

One-dimensional self-assembly of macrocycles is one of the important strategies for constructing fibrous nanomaterials with anisotropic functions such as one-dimensional transport and accumulation of molecules and ions. Herein we report on the synthesis and properties of self-assembled nanofibers using macrocycles to develop a multipurpose template for one-dimensional array of noble metal ions. The nanofibers were prepared by protonation-induced self-assembly of bis-phenanthroline macrocycles, which have enabled the accumulation of some metal-containing anions, such as tetrachloroaurate, hexachloroplatinate and phosphomolybdate. Microscopic observations have demonstrated that the supramolecular nanofibers were reproducibly formed in a similar way, regardless of the structures and charge numbers of the anions. Moreover, the resulting nanofibers, arrayed with several metal ions, were chemically reduced, producing dispersible gold nanoparticles and mixed-valence nanofibers.

Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice.

Background and Purpose: Atherosclerosis is vascular disease of chronic inflammation and lipid disorder, which is a major cause of coronary heart disease. Foam cell formation is key progress during the atherosclerosis development. Insulin-like growth factor (IGF)-1 is a growth hormone that plays a crucial role in growth, metabolism, and homeostasis. Previous studies have demonstrated that increase in circulating IGF-1 can reduce atherosclerotic burden. However, active IGF-1 is characterized with poor tissue retention and is at a very low level in circulation system. Therefore, supplementation of exogenous IGF-1 to restore the physiological level is a promising approach to inhibit atherosclerosis. In this study, we develop a self-assembling, anti-inflammatory drug-modified peptide derived from IGF-1 to mimic IGF-1 bioactivity and simultaneously with an anti-inflammatory property for the treatment of atherosclerosis.Methods: ApoE-/- mice were subcutaneously (s.c.) injected with the different hydrogels or natural IGF-1 protein solution per week and simultaneously fed a high-fat diet for 16 weeks. Atherosclerotic lesion formation and stability were assessed after treatment. Moreover, peritoneal macrophage and serum samples were collected to determine lipid profile and inflammatory cytokines. Concurrently, we determined the effect of bifunctional supramolecular nanofibers/hydrogel on cholesterol efflux, foam cell formation, phenotypic transformation of VSMC to macrophage-like cells, and macrophage polarization in vitro or in vivo.Results: Bifunctional supramolecular nanofibers/hydrogel for the treatment of atherosclerosis was formed by a short peptide consisting of a tetrapeptide SSSR from C-region of growth factor IGF-1, an anti-inflammatory drug naproxen (Npx), and a powerful self-assembling D-peptide DFDF. The resulting hydrogel of Npx-DFDFGSSSR (Hydrogel 1, H1) possessed both the anti-inflammatory and IGF-1 mimicking properties, and it efficiently promoted the expression of ABCA1 and ABCG1, thereby significantly reducing cholesterol accumulation in macrophages and preventing foam cell formation. Moreover, H1 markedly inhibited the transformation of vascular smooth muscle cells (VSMCs) into macrophage-like cells which also contributed to foam cell formation. In addition, H1 significantly reduced the inflammatory response in vitro and in vivo. Most importantly, the IGF-1 mimetic peptide showed comparable performance to IGF-1 in vivo and inhibited atherosclerosis by markedly reducing lesion area and enhancing plaque stability.Conclusions: Our study provides a novel supramolecular nanomaterial to inhibit pathological progress of atherosclerosis through regulating cholesterol efflux and inflammation, which may contribute to the development of a promising nanomedicine for the treatment of atherosclerosis in the clinic.

Compartmentalization within Nanofibers of Double-Decker Phthalocyanine Induces High-Performance Sensing in both Aqueous Solution and the Gas Phase.

The functionalization of natural 1D architectures is dependent on hierarchically inner nanostructures. However, the artificial supramolecular nanofibers or nanotubes were rarely developed with complex inner structures. Inspired by a biomimetic strategy, single-molecule-diameter nanofibers of double-decker phthalocyanine (EuPc2) with compartmentalized internal space and fantastic electrochemical features were developed upon air/water interfacial assembly with poly-l-lysine. EuPc2/poly-l-lysine nanofibers can be electrochemical sensors both in water and the gas phase and have the best analytical performances for nitrite among all the porphyrins or phthalocyanines monomers and assemblies. Imbedding nitrite in compartments not only promotes the sensing but also changes the supramolecular chirality of nanofibers, and the morphological-dependent sensing properties of EuPc2 assemblies in water are different from that in the gas phase. These results suggest the unprecedented properties for diverse applications of artificial 1D architectures containing complex inner nanostructures.

Self-assembled peptide nanostructures targeting death receptor 5 and encapsulating paclitaxel as a multifunctional cancer therapy.

The development of tumor-targeted nanoscale carriers for the delivery of cancer therapeutics offers the ability to increase efficacy while limiting off-target toxicity. In this work we focused on targeting death receptor 5 (DR5), which is highly expressed by cancer cells, and upon binding, triggers programmed cell death. Hence, a nanostructure targeting DR5 would act as a dual targeting and therapeutic agent. We report here on a peptide amphiphile (PA) containing a dimeric, cyclic peptide that self-assembles into cylindrical supramolecular nanofibers and targets DR5. Coassembly of the DR5-targeting PA and a pegylated PA creates a supramolecular nanoscale construct with enhanced binding affinity to DR5 relative to a monomeric targeting PA, and was found to be cytotoxic in vitro. When combined with the chemotherapy paclitaxel, DR5-targeting carriers showed potent antitumor activity in vivo, demonstrating the multifunctional capabilities of peptide-based supramolecular nanostructures.

Effect of Chirality on Cell Spreading and Differentiation: From Chiral Molecules to Chiral Self-Assembly.

The influence of chirality on cell behavior is closely related with relevant biological events; however, many recent studies only focus on the apparent chiral influence of supramolecular nanofibers and ignore the respective effects of molecular chirality and supramolecular chirality in biological processes. Herein, the inherent molecular and supramolecular chiral effects on cell spreading and differentiation are studied. Left-handed nanofibers (referring to supramolecular chirality) assembled from l-amino acid derivatives can enhance cell spreading and proliferation compared to flat l-surfaces (referring to molecular chirality). However, compared to the d-surfaces (referring to molecular chirality), right-handed nanofibers (referring to supramolecular chirality) derived from d-amino acid suppress cell spreading and proliferation, overturning the conventional view that a fibrous morphology generally enhances cell adhesion. The results directly suggest that the amplification of chirality from chiral molecules to chiral assemblies significantly enhances the effect on regulated cell behavior by supramolecular helical handedness. Moreover, cell differentiation is found to be chirality dependent. It suggests that both the l-amino acid derivatives and the left-handed fibers facilitate osteogenic differentiation. This study provides useful insight into understanding the origin of chiral expression from the molecular to the macroscopic level in nature.

Wire‐Like Tip‐To‐Tip Linked Assemblies of CdSe‐CdS Quantum Rods Promoted on Supramolecular Nanofibers of Hybrid Organo‐ and Hydrogels

AbstractA variety of core‐shell CdSe‐CdS nanorods or quantum rods (QRs), both sphere (CdSe) in rod (CdS) and rod (CdSe) in rod (CdS) have been synthesized in a seeded‐growth approach using a very efficient and highly thermally stable steroidal cadmium precursor replacing the more common CdO: cadmium deoxycholate. The core‐shell QRs display high photoluminescence quantum yields (40–75%) and high molar absorption co‐efficient (ϵ=106 M−1 cm−1). Sphere‐in‐rods QRs can be co‐assembled with the organogelator diethylaminolithocholyl iodide in 1,2‐dichlorobenzene and with the hydrogelator calcium cholate in water to form hybrid gels. These organic‐inorganic hybrid soft materials are translucent and brightly red‐luminescent. The nanofibers composing the gel network act as a scaffold to support the dispersed QRs and impede their self‐aggregation. Furthermore, formation of original wire‐like assemblies of the nanorods is promoted in these gels, in particular in the hydrogel. This orientation occurs by a QR tip‐to‐tip interaction and is proposed to be driven by the amphiphilic behaviour of the QRs: laterally capped by negatively charged TGA (thioglycolic acid) ligands and un‐capped on the tips due to TGA unbinding. The combination of nanofiber‐forming hydrogelators and elongated quantum rods is promising in the perspective to form hybrid nanostructures with anisotropic optic or electronic properties.

PH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds

Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

Glycine Substitution Effects on the Supramolecular Morphology and Rigidity of Cell-Adhesive Amphiphilic Peptides.

Self-assembling peptides that are capable of adopting β-sheet structures can generate nanofibers that lead to hydrogel formation. Herein, to tune the supramolecular morphologies, mechanical properties, and stimuli responses of the hydrogels, we investigated glycine substitution in a β-sheet-forming amphiphilic peptide. Glycine substitution generally enhances conformational flexibility. Indeed, glycine substitution in an amphiphilic peptide weakened the hydrogels or even inhibited the gelation. However, unexpectedly, glycine substitution at the center of the peptide molecule significantly enhanced the hydrogel stiffness. The central glycine substitution affected the molecular packing and led to twisted β-sheet structures and to nanofiber bundling, which likely led to the stiffened hydrogel. Importantly, the supramolecular structures were accurately predicted by molecular dynamics simulations, demonstrating the helpfulness of these techniques for the identification of self-assembling peptides. The hydrogel formed by the amphiphilic peptide with the central glycine substitution had cell adhesive function, and showed a reversible thermal gel-to-sol transition. Thus, glycine substitution is effective in modulating self-assembling structures, rheological properties, and dynamics of biofunctional self-assembling peptides.

Membrane-Disrupting Nanofibrous Peptide Hydrogels.

Self-assembled peptide nanofibers can form biomimetic hydrogels at physiological pH and ionic strength through noncovalent and reversible interactions. Inspired by natural antimicrobial peptides, we designed a class of cationic amphiphilic self-assembled peptides (CASPs) that self-assemble into thixotropic nanofibrous hydrogels. These constructs employ amphiphilicity and high terminal charge density to disrupt bacterial membranes. Here, we focus on three aspects of the self-assembly of these hydrogels: (a) the material properties of the individual self-assembled nanofibers, (b) emergence of bulk-scale elasticity in the nanofibrous hydrogel, and (c) trade-off between the desirable material properties and antimicrobial efficacy. The design of the supramolecular nanofibers allows for higher-order noncovalent ionic cross-linking of the nanofibers into a viscoelastic network. We determine the stiffness of the self-assembled nanofibers via the peak force quantitative nanomechanical atomic force microscopy and the bulk-scale rheometry. The storage moduli depend on peptide concentration, ionic strength, and concentration of multivalent ionic cross-linker. CASP nanofibers are demonstrated to be effective against Pseudomonas aeruginosa colonies. We use nanomechanical analysis and microsecond-time scale coarse-grained simulation to elucidate the interaction between the peptides and bacterial membranes. We demonstrate that the membranes stiffen, contract, and buckle after binding to peptide nanofibers, allowing disruption of osmotic equilibrium between the intracellular and extracellular matrix. This is further associated with dramatic changes in cell morphology. Our studies suggest that self-assembled peptide nanofibrils can potentially acts as membrane-disrupting antimicrobial agents, which can be formulated as injectable hydrogels with tunable material properties.

Hofmeister Effects on Peptide Amphiphile Nanofiber Self-Assembly.

Self-assembled peptide amphiphile (PA) nanofibers have emerged as bio-inspired materials with numerous applications in nanotechnology. However, environmental variables, such as salt concentration, pH, or temperature, can greatly impact the self-assembly process. Being able to tune the electrostatic interaction and intermolecular hydrogen bonding is essential in designing stable structures. The ion-specific effects on stabilization of peptides in solution typically follow the Hofmeister series and can be used to control the strength of interaction between ions and PAs. In this study, we performed atomistic molecular dynamics simulations to understand how we can use Hofmeister effects to control PA nanofiber structure. Our results show that the formation of β-sheets in PA nanofibers follows a direct Hofmeister order (F- > Cl- > Br- > I-), resulting from the strong interaction of strongly hydrated ions (F-, Cl-) with the charged amino acid residues on the nanofiber surface. On the other hand, weakly hydrated ions (I-, Br-) interact more preferably with the hydrophobic residues that form the stable β-sheets in the interior of the peptide closer to the core of the nanofiber. We also found that strongly hydrated ions can induce coil to β-sheet transition in the lysine residues close to the nanofiber surface by forming salt bridges between lysine residues of neighboring PA chains. With this work, we provide insight into how the structure of PA nanofibers can be tuned using different salt solutions for developing more stable supramolecular nanofibers for future applications.

Self-Assembled Peptide Nanofibers Display Natural Antimicrobial Peptides to Selectively Kill Bacteria without Compromising Cytocompatibility

One of the major hurdles in the development of antimicrobial peptide (AMP)-based materials is their poor capacity in selectively killing bacteria without harming nearby mammalian cells. Namely, they are antimicrobial but cytotoxic. Current methods of nanoparticle-encapsulated AMPs to target bacteria selectively still have not yet overcome this hurdle. Here, we demonstrate a simple yet effective method to address this daunting challenge by associating a natural AMP with a β-sheet-forming synthetic peptide. The integrated peptides self-assembled to form a supramolecular nanofiber, resulting in the presentation of the AMP at the nanofiber-solvent interface in a precisely controlled manner. Using melittin as a model natural AMP, we found that the conformation of melittin changed dramatically when presented on the nanofiber surface, which, in turn, modulated the induced membrane permeability of the bacterial and mammalian cell membranes. Specifically, the presentation of melittin on the nanofiber restricted its hydrophobic residues, leading to a reduction of the hydrophobic interaction with lipids in the cell membranes. Compellingly, the reduced hydrophobic interaction led to a considerable decrease of melittin's induced permeability of the mammalian cell membrane than that of the bacterial cell membrane. As a result, the AMP-displaying nanofiber preferentially permeabilized and disrupted the membrane of the bacteria without compromising the mammalian cells. Such improved membrane selectivity and cytocompatibility were confirmed in a cell-based membrane localization and live-dead assay. Our new strategy holds great promise for fabricating cytocompatible antimicrobial assemblies that offer safer and more effective administration of therapeutic AMPs. These assemblies, with intrinsic antimicrobial activity and cytocompatibility, can also serve as building blocks for the construction of higher-ordered scaffolds for other biomedical applications such as tissue engineering and regenerative medicine.

Self-adjuvanting properties of peptide nanofiber vaccines are dependent on autophagy

Abstract A crucial challenge in subunit vaccine development is to minimize adjuvant-associated toxicity and balance immunogenicity with safety. Due to the chemical heterogeneity and toxicity associated with most plant- or pathogen-derived adjuvants, those clinically approved in the U.S. are limited to alum and AS04 (alum combined with MPLA). Therefore, there is a compelling clinical need for new adjuvant strategies that potentiate strong immune responses and are chemically defined and minimally toxic. We have previously demonstrated that supramolecular peptide nanofibers are potent adjuvants that elicit protective antibody and cellular immune responses in animal models of infectious diseases, cancer, and addiction. Critically, the adjuvant potential was non-inflammatory and the exact mechanism of action was unknown. Here, we report that self-assembling peptide nanofibers bearing CD4+ or CD8+T cell epitopes are processed through mechanisms of autophagy in antigen presenting cells (APCs). Using in vitro antigen presentation assays, we confirmed loss and gain of adjuvant function using pharmacological modulators of autophagy and APCs deficient in multiple autophagy proteins. Incorporation of microtubule associated protein 1A/1B-light chain 3 (LC3-II) into the autophagosomal membrane, a key biological marker for autophagy, was confirmed using microscopy. Our findings indicate that autophagy plays an essential role in the mechanism of adjuvant action of supramolecular peptide nanofibers.

A comparison of peptide amphiphile nanofiber macromolecular assembly strategies.

Supramolecular peptide nanofibers that are composed of peptide amphiphile molecules have been widely used for many purposes from biomedical applications to energy conversion. The self-assembly mechanisms of these peptide nanofibers also provide convenient models for understanding the self-assembly mechanisms of various biological supramolecular systems; however, the current theoretical models that explain these mechanisms do not sufficiently explain the experimental results. In this study, we present a new way of modeling these nanofibers that better fits with the experimental data. Molecular dynamics simulations were applied to create model fibers using two different layer models and two different tilt angles. Strikingly, the fibers which were modeled to be tilting the peptide amphiphile molecules and/or tilting the plane were found to be more stable and consistent with the experiments.

In Situ Photoconversion of Multicolor Luminescence and Pure White Light Emission Based on Carbon Dot-Supported Supramolecular Assembly.

Constructing multicolor photoluminescence materials that allow for the integration of suitable external stimuli in order to control luminescence color conversions is a challenging objective. Multicolor luminescent output that is regulated in an in situ photo-controlled manner is not a common phenomenon. Herein, a photoluminescent supramolecular assembly, prepared in two stages, is described that displays in situ photo-tuning broad-spectrum output. Benefiting from the reversible photo-switched constitutional interconversion of diarylethenes, the fluorescence of a guest molecule, styrylpyridinium-modified diarylethene, can be switched on/off by alternating ultraviolet and visible light irradiation. Upon complexation of this guest with a host, cucurbit[8]uril, the fluorescence intensity of the resulting binary supramolecular nanofiber shows a drastic enhancement when compared with that of the free guest, which can also be quenched and recovered reversibly by light irradiation. Significantly, such cationic supramolecular nanofibers also interact with anionic carbon dots to form broad-spectrum output ternary supramolecular assemblies, the fluorescence of which can be changed efficiently from yellow to blue in an in situ photo-controlled manner. Pure white light emission can be realized expediently in the luminescence color-conversion process. The use of light as an external stimulus to regulate fluorescent color conversion provides us with an opportunity to design and construct more advanced anti-counterfeiting materials as well as visual display instruments.