De novo amyloid peptides with subtle sequence variations differ in their self-assembly and nanomechanical properties.

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross ß-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications. In order to design customizable and tunable amyloid nanomaterials, it is imperative to understand the sensitivity of the peptide sequence for subtle changes based on amino acid position and chemistry. Here we report our results from four rationally-designed amyloidogenic decapeptides that subtly differ in hydrophobicity and polarity at positions 5 and 6. We show that making the two positions hydrophobic renders the peptide with enhanced aggregation and material properties while introducing polar residues in position 5 dramatically changes the structure and nanomechanical properties of the fibrils formed. A charged residue at position 6, however, abrogates amyloid formation. In sum, we show that subtle changes in the sequence do not make the peptide innocuous but rather sensitive to aggregation, reflected in the biophysical and nanomechanical properties of the fibrils. We conclude that tolerance of peptide amyloid for changes in the sequence, however small they may be, should not be neglected for the effective design of customizable amyloid nanomaterials.

Cationic Glycopolyelectrolytes for RNA Interference in Tick Cells.

The black-legged tick (Ixodes scapularis) is the primary vector for bacteria that cause Lyme disease (Borrelia burgdorferi), where numerous glycosylated tick proteins are involved at the interface of vector-host-pathogen interactions. Reducing the expression of key tick proteins, such as selenoprotein K (SelK), through RNA interference is a promising approach to reduce pathogen transmission, but efficient delivery of nucleic acids to arthropods has proven challenging. While cationic glycopolymers have been used as nonviral gene delivery vehicles in mammalian cells, their use in arthropod or insect gene transfection has not been established. In this study, statistical acrylamide-based cationic glycopolymers with glucose or galactose pendant groups were synthesized by reversible addition-fragmentation chain transfer polymerization, and the effects of the saccharide pendant group and cationic monomer loading on polymer cytotoxicity, RNA complexation, and SelK gene knockdown in ISE6 cells were evaluated. All polymers exhibited low cytotoxicity, yet RNA/copolymer complex cell uptake and gene knockdown were highly dependent on the saccharide structure and the N:P (amino to phosphate groups) ratio.

Synthesis and Morphology of High-Molecular-Weight Polyisobutylene-Polystyrene Block Copolymers Containing Dynamic Covalent Bonds.

Incorporating dynamic covalent bonds into block copolymers provides useful molecular level information during mechanical testing, but it is currently unknown how the incorporation of these units affects the resultant polymer morphology. High-molecular-weight polyisobutylene-b-polystyrene block copolymers containing an anthracene/maleimide dynamic covalent bond are synthesized through a combination of postpolymerization modification, reversible addition-fragmentation chain-transfer polymerization, and Diels-Alder coupling. The bulk morphologies with and without dynamic covalent bond are characterized by atomic force microscopy  and small-angle X-ray scattering, which reveal a strong dependence on annealing time and casting solvent. Morphology is largely unaffected by the inclusion of the mechanophore. The high-molecular-weight polymers synthesized allow interrogation of a large range of polymer domain sizes.

Effects of Stereochemistry and Hydrogen Bonding on Glycopolymer-Amyloid-ß Interactions.

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either ß,d-glucose or ß,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aß42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aß42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aß42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aß42 peptide.

Amyloid peptide - synthetic polymer blends with enhanced mechanical and biological properties.

Interest in utilizing amyloids to develop biomaterials is increasing due to their potential for biocompatibility, unique assembling morphology, mechanical stability, and biophysical properties. However, challenges include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials. In this work, two decapeptides with fibrillar and globular morphologies were selected, blended with poly(ethylene oxide), and fabricated into composite mats via electrospinning. Notable enhancements in mechanical properties were observed, attributed to the uniform distribution of the decapeptide assemblies within the PEO matrix. Morphological differences, such as the production of thinner nanofibers, are attributed to the increased conductivity from the zwitterionic nature of the decapeptides. Blend rheology and post-processing analysis revealed how processing might affect the amyloid aggregation and secondary structure of the peptides. Both decapeptides demonstrated good biocompatibility and strong antioxidant activity, indicating their potential for safe and effective use as biomaterials. By evaluating these interdependencies, this research lays the foundation for understanding the structure-property-processing relationships of peptide-polymer blends and highlights the strong potential for developing applications in biotechnology.

Correction to "ß-Phase Crystallinity, Printability, and Piezoelectric Characteristics of Polyvinylidene Fluoride (PVDF)/Poly(methyl methacrylate) (PMMA)/Cyclopentyl-polyhedral Oligomeric Silsesquioxane (Cp-POSS) Melt-Compounded Blends".

[This corrects the article DOI: 10.1021/acsapm.4c00468.].

ß-Phase Crystallinity, Printability, and Piezoelectric Characteristics of Polyvinylidene Fluoride (PVDF)/Poly(methyl methacrylate) (PMMA)/Cyclopentyl-Polyhedral Oligomeric Silsesquioxane (Cp-POSS) Melt-Compounded Blends.

Poly(vinylidene fluoride) (PVDF) is a semicrystalline polymer that exhibits unique piezoelectric characteristics along with good chemical resistance and high thermal stability. Layer-based material extrusion (MEX) 3D printing of PVDF is desired to create complex structures with piezoelectric properties; however, the melt processing of PVDF typically directs the formation of the α crystalline allomorph, which does not contribute to the piezoelectric response. In this work, PVDF was compounded with poly(methyl methacrylate) (PMMA) and cyclopentyl-polyhedral oligomeric silsesquioxane (Cp-POSS) nanostructured additives in binary and ternary blends to improve MEX printability while maintaining piezoelectric performance. Overall crystallinity and ß phase content were evaluated and quantified using a combination of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Enhancement of MEX printability was measured by quantifying the interlayer adhesion and warpage of printed parts. All blends studied contained a significant percentage of ß allomorph, but it could be detected by ATR-FTIR only after the removal of a thin surface layer. Inclusion of 1% Cp-POSS and up to 10% PMMA in blends with PVDF improved interlayer adhesion (2.3-3.6x) and lowered warpage of MEX printed parts compared to neat PVDF. The blend of 1% Cp-POSS/1% PMMA/PVDF was demonstrated to significantly improve the quality of MEX printed parts while showing similar piezoelectric performance to that of neat PVDF (average piezoelectric coefficient 24 pC/N). MEX printing of PVDF blends directly into usable parts with significant piezoelectric performance while reducing the challenges of printing the semicrystalline polymer opens the potential for application in a number of high value sectors.

Entrepreneurship in Polymer Chemistry.

Launching a startup company is like synthesizing a new molecule. There is a starting point and a general concept for how to achieve the desired end. Known steps may be taken, but a successful synthesis is rarely the result of the original plan and relies on perseverance and creativity. If done well, the starting molecule (idea) gives rise to a new final product (business). Having personally lived these journeys, the authors of this viewpoint distilled their combined experiences into relevant topics for scientific entrepreneurs. This viewpoint is not a how-to guide for launching a startup. Instead, relatable personal insights and potential best practices are shared to catalyze discussions around a topic of growing relevance to both the polymer community and workforce of the future.

Aqueous RAFT Synthesis of Low Molecular Weight Anionic Polymers for Determination of Structure/Binding Interactions with Gliadin.

Gliadin, a component of gluten and a known epitope, is implicated in celiac disease (CeD) and results in an inflammatory response in CeD patients when consumed. Acrylamide-based polyelectrolytes are employed as models to determine the effect of molecular weight and pendent group on non-covalent interaction modes with gliadin in vitro. Poly(sodium 2-acrylamido-2-methylpropane sulfonate) and poly(sodium 3-methylpropyl-3-butanoate) are synthesized via aqueous reversible addition fragmentation chain transfer (aRAFT) polymerization and characterized by gel permeation chromatography-multiangle laser light scattering. The polymer/gliadin blends are examined via circular dichroism, zeta potential measurements, 8-anilinonaphthalene-1-sulfonic acid fluorescence spectroscopy, and dynamic light scattering. Acrylamide polymers containing strong anionic pendent groups have a profound effect on gliadin secondary structure and solution behavior below the isoelectric point, while polymers containing hydrophobic character only have a minor impact. The polymers have little effect on gliadin secondary structure and solution behavior at the isoelectric point.

Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential.

The design of antimicrobial polymers to address healthcare issues and minimize environmental problems is an important endeavor with both fundamental and practical implications. Quaternary ammonium silane-functionalized methacrylate (QAMS) represents an example of antimicrobial macromonomers synthesized by a sol-gel chemical route; these compounds possess flexible Si-O-Si bonds. In present work, a partially hydrolyzed QAMS co-polymerized with 2,2-[4(2-hydroxy 3-methacryloxypropoxy)-phenyl]propane is introduced. This methacrylate resin was shown to possess desirable mechanical properties with both a high degree of conversion and minimal polymerization shrinkage. The kill-on-contact microbiocidal activities of this resin were demonstrated using single-species biofilms of Streptococcus mutans (ATCC 36558), Actinomyces naeslundii (ATCC 12104) and Candida albicans (ATCC 90028). Improved mechanical properties after hydration provided the proof-of-concept that QAMS-incorporated resin exhibits self-repair potential via water-induced condensation of organic modified silicate (ormosil) phases within the polymerized resin matrix.