Supramolecular Nanofibers Research Articles

Phenyl groups in supramolecular nanofibers confer hydrogels with high elasticity and rapid recovery

In this study, we report multi-component supramolecular hydrogels that exhibit exceptional high storage moduli and a rapid recovery of their original mechanical strength after removing external forces. The formation of such kind of supramolecular hydrogels is simple and versatile, and the components can be easily synthesized or commercially available in large quantities. The supramolecular hydrogels have been characterized by SEM and fluorescence spectrometry and the results obtained by both techniques correlate well with their mechanical properties. They have potential to be developed into useful materials that require high mechanical stiffness and possess rapid recovery properties, such as the injectable immobilization matrix for cells culture, drug release, enzyme encapsulation, etc.

Supramolecular hydrogel-based protein and chemosensor array

The development of protein and sensor arrays is crucial for rapid and high-throughput assays of biological events, markers, environmental pollutants, and others. We describe supramolecular hydrogel as a unique material for use as a matrix for immobilizing proteins, peptides, substrates, chemosensors, and mesoporous silica particles, and thereby array them on solid supports. The semi-wet conditions provided by the gel, which consists of 3D supramolecular nanofiber network structure, are suitable for entrapping such substances whilst retaining their activity and function. Moreover, the hydrophobic interior of the nanofibers of the supramolecular hydrogel can reversibly entrap hydrophobic molecules, which allows the development of various read-out systems, such as fluorescence enhancement and fluorescence resonance energy transfer (FRET), by which one can monitor the signal changes associated with, for instance, molecular recognition and enzyme activity.

Supramolecular hydrogel capsule showing prostate specific antigen-responsive function for sensing and targeting prostate cancer cells

A supramolecular hydrogel 1, prepared at high concentration (5–10 wt%), exhibited mechanical toughness comparable to that of a polymer hydrogel, even though the gel was constructed solely by noncovalent bonding interactions among small molecules. The mechanical toughness and thermal reversibility of gel 1 allowed us to fabricate a supramolecular hydrogel capsule (SH-capsule) 1 which was easily handled and was stable in aqueous and cell culture media. The mechanical and substance-release/uptake properties of SH-capsule 1 were investigated by atomic force microscope (AFM) indentation, fluorescence spectroscopy, and confocal laser scanning microscopy (CLSM). On the basis of those properties we successfully designed an enzyme- and cell-responsive SH-capsule. To install a function of enzyme-responsive substance release into the SH-capsule 1, enzyme-labile, amphiphilic additive 2 was embedded in supramolecular nanofibers of 1 through a supramolecular co-assembly method. As a proof-of-concept, we constructed the functional SH-capsule 1/2 that can release a model fluorescent drug triggered by prostate specific antigen (PSA)-catalyzed proteolysis. Selective release of the fluorescent substance was exploited to both assay PSA activity and detect prostate cancer (PCa) cells. We also clearly demonstrated that the released fluorescent substance was delivered and internalized into the PCa cells, mediated by binding to the membrane-bound protein prostate-specific membrane antigen (PSMA), which is over-expressed on a plasma membrane of the PCa cells.

Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers

Biomaterials that promote angiogenesis have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosaminoglycans were evaluated here using a dorsal skinfold chamber model to dynamically monitor the interaction between the nanofiber gel and the microcirculation, representing a novel application of this model. We paired this model with a conventional subcutaneous implantation model for static histological assessment of the interactions between the gel and host tissue. In the static analysis, the heparan sulfate-containing nanofiber gels were found to persist in the tissue for up to 30 days and revealed excellent biocompatibility. Strikingly, as the nanofiber gel biodegraded, we observed the formation of a de novo vascularized connective tissue. In the dynamic experiments using the dorsal skinfold chamber, the material again demonstrated good biocompatibility, with minimal dilation of the microcirculation and only a few adherent leukocytes, monitored through intravital fluorescence microscopy. The new application of the dorsal skinfold model corroborated our findings from the traditional static histology, demonstrating the potential use of this technique to dynamically evaluate the biocompatibility of materials. The observed biocompatibility and development of new vascularized tissue using both techniques demonstrates the potential of these angiogenesis-promoting materials for a host of regenerative strategies.

Evidence of induced chirality in stirred solutions of supramolecular nanofibers

Two-modulator generalized ellipsometry is used to determine the spectroscopic Mueller matrix of a solution of porphyrin supramolecular aggregates that have fibrous form. During the measurements the solutions were stirred in clockwise and anticlockwise directions. The pseudopolar decompostion is applied to the experimental Mueller matrices to unveil the birefringent and dichroics properties of the sample. The vortex flow in the stirred solution is found to modify the optical response of the aggregates to polarized light, and, in particular, its chiral signature is determined by the stirring direction in a totally reversible process. The data found show that chirality can be induced by stirring in solutions of supramolecular fibers and that a effective transfer of chirality from a macroscopic phenomenon to the supramolecular structures takes place.

Bioactive Nanostructures for Regeneration

Bioactive nanostructures molecularly crafted to signal cells or deliver cargo to specific cells have great potential to regenerate tissues and cure disease. The chemistry of such nanostructures should allow them to interact specifically with cell receptors or intracellular structures. Ideally, they should also disintegrate into nutrients within an appropriate time frame. The organization of these nanostructures at larger length scales comparable to cells and large colonies of cells will also be critical for their function. Our laboratory has developed an extensive family of amphiphilic molecules that self‐assemble into supramolecular nanofibers with the capacity to display a large diversity of signals to cells1‐5. Using both polymers and small molecules we have also developed macroscopic constructs that can organize or confine cells in three dimensions. This lecture will illustrate the use of these systems to regenerate axons in the central nervous system for spinal cord injuries, to promote angiogenesis in cardiovascular therapies, induce bone formation, and mediate the differentiation of stem cells.

Bio‐based nanocomposites composed of photo‐cured epoxidized soybean oil and supramolecular hydroxystearic acid nanofibers

AbstractA mixture of epoxidized soybean oil (ESO), (R)‐12‐hydroxystrearic acid (HSA) and a photoinitiator for cationic polymerization in the ESO/HSA weight ratio 10/1 was heated to 100 °C and gradually cooled to room temperature to give bio‐based gelatinous material. The photo‐curing of the gel afforded a nanocomposite composed of crosslinked ESO and supramolecular HSA nanofibers. The transmission electron microscopy observation of the photo‐cured ESO/HSA revealed that dendritic clusters of HSA nanofibers are formed in the crosslinked ESO matrix. In the differential scanning calorimetry chart of the ESO/HSA, a thermal transition from the mesophase composed of supramolecular nanofibers to isotropic state was observed at 67 °C (ΔH = 22.6 J/g‐HSA), while the Tm of crystalline HSA is 77.7 °C (ΔHm = 159 J/g‐HSA). Tensile strength at 20 °C of the ESO‐HSA was ∼80% higher than that of photo‐cured ESO without HSA. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 669–673, 2009

Three-Dimensional Encapsulation of Live Cells by Using a Hybrid Matrix of Nanoparticles in a Supramolecular Hydrogel

From a library of glyco-lipid mimics with muconic amide as the spacer, we found that 1, a glyco-lipid that has N-acetyl glucosamine and methyl cyclohexyl groups as its hydrophilic head and hydrophobic tails, respectively, formed a stable hydrogel (0.05 wt %) through hierarchical self-assembly of the lipid molecules into supramolecular nanofibers. The formation of the supramolecular hydrogel was verified by rheological measurements, and the supramolecular nanofiber was characterized as the structural element by transmission electron microscopy and atomic force microscopy observations. Absorption and circular dichroism spectroscopic measurements revealed that the muconic amide moieties of 1 are arranged in a helical, stacked fashion in the self-assembled nanofibers. Moreover, we unexpectedly found that the homogeneous distribution of the supramolecular nanofibers of 1 was greatly facilitated by the addition of polystyrene nanobeads (100-500 nm in diameter), as evaluated by confocal laser scanning microscopic observations. It is interesting that the obtained supramolecular hybrid matrix can efficiently encapsulate and distribute live Jurkat cells in three dimensions under physiological conditions. This supramolecular hybrid matrix is intriguing as a unique biomaterial.

Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury.

Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.

Peptide amphiphile nanofibers with conjugated polydiacetylene backbones in their core.

The coupling of electronic and biological functionality through self-assembly is an interesting target in supramolecular chemistry. We report here on a set of diacetylene-derivatized peptide amphiphiles (PAs) that react to form conjugated polydiacetylene backbones following self-assembly into cylindrical nanofibers. The polymerization reaction yields highly conjugated backbones when the peptidic segment of the PAs has a linear, as opposed to a branched, architecture. Given the topotactic nature of the polymerization, these results suggest that a high degree of internal order exists in the supramolecular nanofibers formed by the linear PA. On the basis of microscopy, the formation of a polydiacetylene backbone to covalently connect the beta-sheets that help form the fibers does not disrupt the fiber shape. Interestingly, we observe the appearance of a polydiacetylene (PDA) circular dichroism band at 547 nm in linear PA nanofibers suggesting the conjugated backbone in the core of the nanostructures is twisted. We believe this CD signal is due to chiral induction by the beta-sheets, which are normally twisted in helical fashion. Heating and cooling shows simultaneous changes in beta-sheet and conjugated backbone structure, indicating they are both correlated. At the same time, poor polymerization in nanofibers formed by branched PAs indicates that less internal order exists in these nanostructures and, as expected, then a circular dichroism signal is not observed for the conjugated backbone. The general variety of materials investigated here has the obvious potential to couple electronic properties and in vitro bioactivity. Furthermore, the polymerization of monomers in peptide amphiphile assemblies by a rigid conjugated backbone also leads to mechanical robustness and insolubility, two properties that may be important for the patterning of these materials at the cellular scale.

Nanofiber formation from sequence-selective DNA-templated self-assembly of a thymidylic acid-appended bolaamphiphile

Quaternary self-assembly of a thymidylic acid-appended bolaamphiphile, with heteropolymeric DNA as a template, produced supramolecular helical nanofibers in the presence of specific target DNA.

Intracellular Enzymatic Formation of Nanofibers Results in Hydrogelation and Regulated Cell Death

Enzymatic formation of supramolecular nanofibers is demonstrated as a novel approach to induce intracellular hydrogelation and control the fate of cells or cellular functions, which can lead to a new paradigm for developing biomaterials to manage cellular artificial nanostructures (CAN), understand cellular functions beyond the molecular level, and create novel therapeutics.

Supramolecular crafting of cell adhesion

The supramolecular design of bioactive artificial extracellular matrices to control cell behavior is of critical importance in cell therapies and cell assays. Most previous work in this area has focused on polymers or monolayers which preclude control of signal density and accessibility in the nanoscale filamentous environment of natural matrices. We have used here self-assembling supramolecular nanofibers that display the cell adhesion ligand RGDS at van der Waals density to cells. Signal accessibility at this very high density has been varied by changes in molecular architecture and therefore through the supramolecular packing of monomers that form the fibers. We found that branched architectures of the monomers and the consequent lower packing efficiency and additional space for epitope motion improves signaling for cell adhesion, spreading, and migration. The use of artificial matrices with nanoscale objects with extremely high epitope densities could facilitate receptor clustering for signaling and also maximize successful binding between ligands and receptors at mobile three-dimensional interfaces between matrices and cells. Supramolecular design of artificial bioactive extracellular matrices to tune cell response may prove to be a powerful strategy in regenerative medicine and to study biological processes.

Supramolecular Nanofibers by Self‐Organization of Bola‐amphiphiles through a Combination of Hydrogen Bonding and π–π Stacking Interactions

Supramolecular nanofibers are formed from aqueous solutions of a bola- amphihile, containing two carboxylic end groups and a central π–π-stacking moiety. The combined noncovalent interactions form the basis for the successful self-assembly of the fibers. The obtained fibers (see figure), with widths on the nanometer scale and lengths of several micrometers or more, exhibit good thermal stability and interesting emittance properties.

β-1,3-Glucan Polysaccharide (Schizophyllan) Acting as a One-Dimensional Host for Creating Supramolecular Dye Assemblies

We have demonstrated that one-dimensional supramolecular dye assemblies with a uniform diameter can be created by utilizing schizophyllan (SPG) as a one-dimensional host. In the supramolecular nanofibers, the dye molecules are assembled into the different aggregation modes depending on the preparation procedures. The findings establish that SPG is useful for creating the supramolecular nanofibers, where temporal superstructures can be stabilized by the SPG-specific helical higher-order structure. [structure: see text].

Intermolecular Forces in the Self‐Assembly of Peptide Amphiphile Nanofibers

AbstractPeptide amphiphile molecules (PAs) developed in our laboratory self‐assemble from aqueous media into three‐dimensional networks of bioactive nanofibers. Multiple non‐covalent interactions promote assembly of the supramolecular nanofibers and ultimately determine the bulk physical properties of the macroscopic gels. In this study, we use oscillatory rheology, Fourier‐transform infrared spectroscopy, and circular‐dichroism spectroscopy to better understand the assembly mechanism of a typical PA molecule known as PA‐1. Self‐assembly of PA‐1 is triggered by counterion screening and stabilized by van der Waals and hydrophobic forces, ionic bridging, and coordination and hydrogen bonding. The concentration, electronic structure, and hydration of counterions significantly influence self‐assembly and gel mechanical properties.

Presentation and Recognition of Biotin on Nanofibers Formed by Branched Peptide Amphiphiles

A branched peptide amphiphile system was designed for enhanced recognition of biotin on nanofibers formed by self-assembly of these molecules. Branching at a lysine residue was used to design peptide amphiphiles that are capable of presenting more than one epitope per molecule. We found that biotinylated branched structures form nanofibers that enhance recognition by the avidin protein receptor relative to similar nanostructures formed by linear peptide analogues. Biotin-avidin binding to the supramolecular nanofibers was characterized by measurement of fluorescence from nanofibers incubated with chromophore-conjugated avidin.

Assembling of amphiphilic highly branched molecules in supramolecular nanofibers.

We found that the amplification of weak multiple interactions between numerous peripheral branches of irregular, flexible, polydisperse, and highly branched molecules can facilitate their self-assembly into nanofibrillar micellar structures at solid surfaces and the formation of perfect long microfibers in the course of crystallization from solution. The core-shell architecture of the amphiphilic dendritic molecules provides exceptional stability of one-dimensional nanofibrillar structures. The critical condition for the formation of the nanofibrillar structures is the presence of both alkyl tails in the outer shell and amine groups in the core/inner shell. The multiple intermolecular hydrogen bonding and polar interactions between flexible cores stabilize these nanofibers and make them robust albeit flexible. This example demonstrates that one-dimensional supramolecular assembling at different spatial scales (both nanofibers and microfibers) can be achieved without a tedious, multistep synthesis of shape-persistent molecules.