Boosting chondrocyte bioactivity with ultra-sulfated glycopeptide supramolecular polymers.

Although autologous chondrocyte transplantation can be effective in articular cartilage repair, negative side effects limit the utility of the treatment, such as long recovery times, poor engraftment or chondrogenic dedifferentiation, and cell leakage. Peptide-based supramolecular polymers have emerged as promising bioactive systems to promote tissue regeneration through cell signaling and dynamic behavior. We report here on the development of a series of glycopeptide amphiphile supramolecular nanofibers with chondrogenic bioactivity.

Biopolymer-supramolecular polymer hybrids for photocatalytic hydrogen production.

Solar generation of H is a promising strategy for dense energy storage. Supramolecular polymers composed of chromophore amphiphile monomers containing perylene monoimide (PMI) have been reported as crystalline light-harvesting assemblies for aqueous H-evolving catalysts. Gelation of these supramolecular polymers with multivalent ions creates hydrogels with high diffusivity but insufficient mechanical stability and catalyst retention for reusability.

Supramolecular Motion Enables Chondrogenic Bioactivity of a Cyclic Peptide Mimetic of Transforming Growth Factor-β1.

Transforming growth factor (TGF)-β1 is a multifunctional protein that is essential in many cellular processes that include fibrosis, inflammation, chondrogenesis, and cartilage repair. In particular, cartilage repair is important to avoid physical disability since this tissue does not have the inherent capacity to regenerate beyond full development. We report here on supramolecular coassemblies of two peptide amphiphile molecules, one containing a TGF-β1 mimetic peptide, and another which is one of two constitutional isomers lacking bioactivity.

Self-Sorting vs Coassembly in Peptide Amphiphile Supramolecular Nanostructures.

The functionality of supramolecular nanostructures can be expanded if systems containing multiple components are designed to either self-sort or mix into coassemblies. This is critical to gain the ability to craft self-assembling materials that integrate functions, and our understanding of this process is in its early stages. In this work, we have utilized three different peptide amphiphiles with the capacity to form β-sheets within supramolecular nanostructures and found binary systems that self-sort and others that form coassemblies.

Hybrid Bonding Bottlebrush Polymers Grafted from a Supramolecular Polymer Backbone.

Bottlebrush polymers, macromolecules consisting of dense polymer side chains grafted from a central polymer backbone, have unique properties resulting from this well-defined molecular architecture. With the advent of controlled radical polymerization techniques, access to these architectures has become more readily available. However, synthetic challenges remain, including the need for intermediate purification, the use of toxic solvents, and challenges with achieving long bottlebrush architectures due to backbone entanglements.

Single-cell coating with biomimetic extracellular nanofiber matrices.

Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments.

Autonomous hydrogel locomotion regulated by light and electric fields.

Autonomous robotic functions in materials beyond simple stimulus-response actuation require the development of functional soft matter that can complete well-organized tasks without step-by-step control. We report the design of photo- and electroactivated hydrogels that can capture and deliver cargo, avoid obstacles, and return without external, stepwise control. By incorporating two spiropyran monomers with different chemical substituents in the hydrogel, we created chemically random networks that enabled photoregulated charge reversal and autonomous behaviors under a constant electric field.

Role of supramolecular polymers in photo-actuation of spiropyran hydrogels.

Supramolecular-covalent hybrid polymers have been shown to be interesting systems to generate robotic functions in soft materials in response to external stimuli. In recent work supramolecular components were found to enhance the speed of reversible bending deformations and locomotion when exposed to light. The role of morphology in the supramolecular phases integrated into these hybrid materials remains unclear.

Supramolecular Nanofibers Block SARS-CoV-2 Entry into Human Host Cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) on host cells to initiate cellular entry. Blocking the interactions between the spike protein and ACE2 offers promising therapeutic opportunities to prevent infection. We report here on peptide amphiphile supramolecular nanofibers that display a sequence from ACE2 in order to promote interactions with the SARS-CoV-2 spike receptor binding domain.

Heterocyclic Chromophore Amphiphiles and their Supramolecular Polymerization.

Supramolecular polymerization of π-conjugated amphiphiles in water is an attractive approach to create functional nanostructures. Here, we report on the synthesis, optoelectronic and electrochemical properties, aqueous supramolecular polymerization, and conductivity of polycyclic aromatic dicarboximide amphiphiles. The chemical structure of the model perylene monoimide amphiphile was modified with heterocycles, essentially substituting one fused benzene ring with thiophene, pyridine or pyrrole rings.

Machine learning overcomes human bias in the discovery of self-assembling peptides.

Peptide materials have a wide array of functions, from tissue engineering and surface coatings to catalysis and sensing. Tuning the sequence of amino acids that comprise the peptide modulates peptide functionality, but a small increase in sequence length leads to a dramatic increase in the number of peptide candidates. Traditionally, peptide design is guided by human expertise and intuition and typically yields fewer than ten peptides per study, but these approaches are not easily scalable and are susceptible to human bias.

Peptide Sequence Determines Structural Sensitivity to Supramolecular Polymerization Pathways and Bioactivity.

Pathways in supramolecular polymerization traverse different regions of the system's energy landscape, affecting not only their architectures and internal structure but also their functions. We report here on the effects of pathway selection on polymerization for two isomeric peptide amphiphile monomers with amino acid sequences AAEE and AEAE. We subjected the monomers to five different pathways that varied in the order they were exposed to electrostatic screening by electrolytes and thermal annealing.

Hybrid Nanocrystals of Small Molecules and Chemically Disordered Polymers.

Organic crystals formed by small molecules can be highly functional but are often brittle or insoluble structures with limited possibilities for use or processing from a liquid phase. A possible solution is the nanoscale integration of polymers into organic crystals without sacrificing long-range order and therefore function. This enables the organic crystals to benefit from the advantageous mechanical and chemical properties of the polymeric component.

Acid-Base Equilibrium and Dielectric Environment Regulate Charge in Supramolecular Nanofibers.

Peptide amphiphiles are a class of molecules that can self-assemble into a variety of supramolecular structures, including high-aspect-ratio nanofibers. It is challenging to model and predict the charges in these supramolecular nanofibers because the ionization state of the peptides are not fixed but liable to change due to the acid-base equilibrium that is coupled to the structural organization of the peptide amphiphile molecules. Here, we have developed a theoretical model to describe and predict the amount of charge found on self-assembled peptide amphiphiles as a function of pH and ion concentration.

Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential.

Supramolecular peptide chemistry offers a versatile strategy to create chemical systems useful as new biomaterials with potential to deliver nearly 1000 known candidate peptide therapeutics or integrate other types of bioactivity. We report here on the co-assembly of lipidated β-sheet-forming peptides with soluble short peptides, yielding with various degrees of internal order. At low peptide concentrations, the co-monomer is protected by lodging within internal aqueous compartments and stabilizing internal β-sheets formed by the lipidated peptides.

Modeling Interactions within and between Peptide Amphiphile Supramolecular Filaments.

Many peptides are able to self-assemble into one-dimensional (1D) nanostructures, such as cylindrical fibers or ribbons of variable widths, but the relationship between the morphology of 1D objects and their molecular structure is not well understood. Here, we use coarse-grained molecular dynamics (CG-MD) simulations to study the nanostructures formed by self-assembly of different peptide amphiphiles (PAs). The results show that ribbons are hierarchical superstructures formed by laterally assembled cylindrical fibers.

Supramolecular Interactions and Morphology of Self-Assembling Peptide Amphiphile Nanostructures.

The morphology of supramolecular peptide nanostructures is difficult to predict given their complex energy landscapes. We investigated peptide amphiphiles containing β-sheet forming domains that form twisted nanoribbons in water. We explained the morphology based on a balance between the energetically favorable packing of molecules in the center of the nanostructures, the unfavorable packing at the edges, and the deformations due to packing of twisted β-sheets.

Hybrid gels bulk interfacial complexation of supramolecular polymers and polyelectrolytes.

Hierarchical self-assembly leading to organized supramolecular structures across multiple length scales has been of great recent interest. Earlier work from our laboratory reported the complexation of peptide amphiphile (PA) supramolecular polymers with oppositely charged polyelectrolytes into a single solid membrane at a macroscopic interface. We report here the formation of bulk gels with many internal interfaces between the covalent and supramolecular polymer components formed by the rapid chaotic mixing of solutions, one containing negatively charged PA nanofibers and the other the positively charged biopolymer chitosan.

Growth of Extra-Large Chromophore Supramolecular Polymers for Enhanced Hydrogen Production.

The control of morphology in bioinspired chromophore assemblies is key to the rational design of functional materials for light harvesting. We investigate here morphological changes in perylene monoimide chromophore assemblies during thermal annealing in aqueous environments of high ionic strength to screen electrostatic repulsion. We found that annealing under these conditions leads to the growth of extra-large ribbon-shaped crystalline supramolecular polymers of widths from about 100 nm to several micrometers and lengths from 1 to 10 μm while still maintaining a unimolecular thickness.

Self-sorting in supramolecular assemblies.

Supramolecular self-assembly enables living organisms to form highly functional hierarchical structures with individual components self-organized across multiple length scales. This has inspired work on multicomponent supramolecular materials to understand factors behind co-assembly versus self-sorting of molecules. We report here on a supramolecular system comprised of negatively charged peptide amphiphile (PA) molecules, in which only a tiny fraction of the molecules (0.

Transforming Growth Factor β-1 Binding by Peptide Amphiphile Hydrogels.

Supramolecular biomaterials are promising systems to bind or deliver therapeutic growth factors given their great structural versatility and tunability of properties by simply mixing molecules. In this work, we have investigated this approach for the growth factor cytokine TGFβ-1, which is potentially important in the regeneration of damaged cartilage or in the prevention of fibrinogenesis of organs and the progression of tumors. Our previous work identified a peptide sequence capable of binding TGFβ-1 and supramolecular peptide amphiphile (PA) nanofiber hydrogels that displayed the sequence were found to enhance regeneration of cartilage in a rabbit model.

Fast and programmable locomotion of hydrogel-metal hybrids under light and magnetic fields.

The design of soft matter in which internal fuels or an external energy input can generate locomotion and shape transformations observed in living organisms is a key challenge. Such materials could assist in productive functions that may range from robotics to smart management of chemical reactions and communication with cells. In this context, hydrated matter that can function in aqueous media would be of great interest.