Designing spin-textured flat bands in twisted graphene multilayers via helimagnet encapsulation

Twisted graphene multilayers provide tunable platforms to engineer flat bands and exploit the associated strongly correlated physics. The two-dimensional nature of these systems makes them suitable for encapsulation by materials that break specific symmetries. In this context, recently discovered two-dimensional helimagnets, such as the multiferroic monolayer NiI2, are specially appealing for breaking time-reversal and inversion symmetries due to their nontrivial spin textures. Here we show that this spin texture can be imprinted on the electronic structure of twisted bilayer graphene by proximity effect. We discuss the dependence of the imprinted spin texture on the wave-vector of the helical structure, and on the strength of the effective local exchange field. Based on these results we discuss the nature of the superconducting instabilities that can take place in helimagnet encapsulated twisted bilayer graphene. Our results put forward helimagnetic encapsulation as a powerful way of designing spin-textured flat band systems, providing a starting point to engineer a new family of correlated moire states.

Role of helical structure and dynamics in oligoadenylate synthetase 1 (OAS1) mismatch tolerance and activation by short dsRNAs

The 2’-5’-oligoadenylate synthetases (OAS) are innate immune sensors of cytosolic double-stranded RNA (dsRNA) that play a critical role in limiting viral infection. How these proteins are able to avoid aberrant activation by cellular RNAs is not fully understood, but adenosine-to-inosine (A-to-I) editing has been proposed to limit accumulation of endogenous RNAs that might otherwise cause stimulation of the OAS/RNase L pathway. Here, we aim to uncover whether and how such sequence modifications can restrict the ability of short, defined dsRNAs to activate the single-domain form of OAS, OAS1. Unexpectedly, we find that all tested inosine-containing dsRNAs have an increased capacity to activate OAS1, whether in a destabilizing (I•U) or standard Watson–Crick-like base pairing (I–C) context. Additional variants with strongly destabilizing A•C mismatches or stabilizing G–C pairs also exhibit increased capacity to activate OAS1, eliminating helical stability as a factor in the relative ability of the dsRNAs to activate OAS1. Using thermal difference spectra and molecular dynamics simulations, we identify both increased helical dynamics and specific local changes in helical structure as important factors in the capacity of short dsRNAs to activate OAS1. These helical features may facilitate more ready adoption of the distorted OAS1-bound conformation or stabilize important structures to predispose the dsRNA for optimal binding and activation of OAS1. These studies thus reveal the molecular basis for the greater capacity of some short dsRNAs to activate OAS1 in a sequence-independent manner.

Helical structure motifs made searchable for functional peptide design

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/.

Thermodynamic surprises of Cu(II)–amylin analogue complexes in membrane mimicking solutions

Membrane environment often has an important effect on the structure, and therefore also on the coordination mode of biologically relevant metal ions. This is also true in the case of Cu(II) coordination to amylin analogues—rat amylin, amylin1–19, pramlintide and Ac-pramlintide, which offer N-terminal amine groups and/or histidine imidazoles as copper(II) anchoring sites. Complex stabilities are comparable, with the exception of the very stable Cu(II)–amylin1–19, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding. Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.

Broadband wavelength tuning of electrically stretchable chiral photonic gel

Chiral photonic-band structure provides technical benefits in the form of a self-assembled helical structure and further functional wavelength tunability that exploits helical deformation according to pitch changes. The stopband wavelength control of the chiral photonic-band structure can be obtained by individual electrical methods or mechanical stretching deformation approaches. However, research on combined electric control of stretchable chiral photonic-band wavelength control while ensuring optical stability during the tuning process has remained limited till now. In this study, using the hybrid structure of elastomeric mesogenic chiral photonic gels (CPGs) with an electrically controlled dielectric soft actuator, we report the first observation of electrically stretchable CPGs and their electro-mechano-optical behaviors. The reliable wavelength tuning of a CPG to a broadband wavelength of ∼171 nm changed with high optical stability and repeated wavelength transitions of up to 100 times. Accordingly, for the first time, electrical wavelength tuning method of stretchable chiral liquid crystal photonicband structure was investigated.

Shack-Hartmann Wavefront Sensing of Ultrashort Optical Vortices

Light beams carrying Orbital Angular Momentum (OAM), also known as optical vortices (OV), have led to fascinating new developments in fields ranging from quantum communication to novel light–matter interaction aspects. Even though several techniques have emerged to synthesize these structured-beams, their detection, in particular, single-shot amplitude, wavefront, and modal content characterization, remains a challenging task. Here, we report the single-shot amplitude, wavefront, and modal content characterization of ultrashort OV using a Shack-Hartmann wavefront sensor. These vortex beams are obtained using spiral phase plates (SPPs) that are frequently used for high-intensity applications. The reconstructed wavefronts display a helical structure compatible with the topological charge induced by the SPPs. We affirm the accuracy of the optical field reconstruction by the wavefront sensor through an excellent agreement between the numerically backpropagated and experimentally obtained intensity distribution at the waist. Consequently, through Laguerre–Gauss (LG) decomposition of the reconstructed fields, we reveal the radial and azimuthal mode composition of vortex beams under different conditions. The potential of our method is further illustrated by characterizing asymmetric Gaussian vortices carrying fractional average OAM, and a realtime topological charge measurement at a 10Hz repetition rate. These results can promote Shack-Hartmann wavefront sensing as a single-shot OV characterization tool.

Design, synthesis, and structural characterization of helix-forming aliphatic homo-δ-peptides based on conformational restriction due to the structural characteristics of cyclopropane

Considerable effort has been directed toward developing artificial peptide-based oligomers that fold into a specific secondary structure, i.e., peptide foldamers. To date, however, detailed structural analysis of crystals of δ-peptide foldamers consisting of aliphatic δ-amino acids, which have a more extended carbon backbone compared with well-studied β- and γ-amino acids, have not been reported. We rationally designed aliphatic homo-δ-peptide foldamers forming a stable helical structure utilizing a chiral cyclopropane δ-amino acid as a monomer unit whose conformation was tightly restricted by the structural characteristics of cyclopropane depending on its stereochemistry. We stereoselectively synthesized the cyclopropane δ-amino acid monomer and prepared its various homo-oligomers. Structural analysis of the homo-δ-peptides using nuclear magnetic resonance, circular dichroism, and infrared spectroscopy revealed that they form a stable 14-helical structure in solution. Furthermore, the effective conformational regulation of the backbone due to the characteristics of cyclopropane allowed us to achieve X-ray crystallographic analysis of the homo-δ-peptides, showing their common right-handed 14-helical structures. The helical structures were consistent with both those predicted by theoretical calculations and those obtained based on nuclear magnetic resonance spectroscopy in solution. A critical point is that the helical structures of these δ-peptides are theoretically predictable by calculations. To our knowledge, this is the first example of aliphatic homo-δ-peptide foldamers forming a stable helical structure both in solution and in crystal.

Stapled Anoplin as an Antibacterial Agent

Anoplin is a linear 10-amino acid amphipathic peptide (Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH2) derived from the venom sac of the solitary wasp. It has broad antimicrobial activity, including an antibacterial one. However, the inhibition of bacterial growth requires several dozen micromolar concentrations of this peptide. Anoplin is positively charged and directly interacts with anionic biological membranes forming an α-helix that disrupts the lipid bilayer. To improve the bactericidal properties of anoplin by stabilizing its helical structure, we designed and synthesized its analogs with hydrocarbon staples. The staple was introduced at two locations resulting in different charges and amphipathicity of the analogs. Circular dichroism studies showed that all modified anoplins adopted an α-helical conformation, both in the buffer and in the presence of membrane mimics. As the helicity of the stapled anoplins increased, their stability in trypsin solution improved. Using the propidium iodide uptake assay in Escherichia coli and Staphylococcus aureus, we confirmed the bacterial membrane disruption by the stapled anoplins. Next, we tested the antimicrobial activity of peptides on a range of Gram-negative and Gram-positive bacteria. Finally, we evaluated peptide hemolytic activity on sheep erythrocytes and cytotoxicity on human embryonic kidney 293 cells. All analogs showed higher antimicrobial activity than unmodified anoplin. Depending on the position of the staple, the peptides were more effective either against Gram-negative or Gram-positive bacteria. Anoplin[5-9], with a lower positive charge and increased hydrophobicity, had higher activity against Gram-positive bacteria but also showed hemolytic and destructive effects on eukaryotic cells. Contrary, anoplin[2-6] with a similar charge and amphipathicity as natural anoplin effectively killed Gram-negative bacteria, also pathogenic drug-resistant strains, without being hemolytic and toxic to eukaryotic cells. Our results showed that anoplin charge, amphipathicity, and location of hydrophobic residues affect the peptide destructive activity on the cell wall, and thus, its antibacterial activity. This means that by manipulating the charge and position of the staple in the sequence, one can manipulate the antimicrobial activity.

Thermodynamic Surprises of Cu(II)-Amylin Complexes in Membrane Mimicking Solutions

Membrane environment often has an important effect on the structure, and therefore also on the coordination mode of biologically relevant metal ions.This is also true in the case of Cu(II) coordination to amylin analogues – rat amylin, amylin1-19, pramlintide and Ac-pramlintide, which offer N-terminal amine groups and/or histidine imidazoles as copper(II) anchoring sites. Complex stabilities are comparable, with the exception of the very stable Cu(II)-amylin1-19, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding.Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.