Heterogeneous and Cooperative Rupture of Histidine-Ni Metal-Coordination Bonds on Rationally Designed Protein Templates.

Metal-coordination bonds, a highly tunable class of dynamic noncovalent interactions, are pivotal to the function of a variety of protein-based natural materials and have emerged as binding motifs to produce strong, tough, and self-healing bioinspired materials. While natural proteins use clusters of metal-coordination bonds, synthetic materials frequently employ individual bonds, resulting in mechanically weak materials. To overcome this current limitation, we rationally designed a series of elastin-like polypeptide templates with the capability of forming an increasing number of intermolecular histidine-Ni metal-coordination bonds.

Delivering on the promise of recombinant silk-inspired proteins for drug delivery.

Effective drug delivery is essential for the success of a medical treatment. Polymeric drug delivery systems (DDSs) are preferred over systemic administration of drugs due to their protection capacity, directed release, and reduced side effects. Among the numerous polymer sources, silks and recombinant silks have drawn significant attention over the past decade as DDSs.

Discovering design principles of collagen molecular stability using a genetic algorithm, deep learning, and experimental validation.

Collagen is the most abundant structural protein in humans, providing crucial mechanical properties, including high strength and toughness, in tissues. Collagen-based biomaterials are, therefore, used for tissue repair and regeneration. Utilizing collagen effectively during materials processing ex vivo and subsequent function in vivo requires stability over wide temperature ranges to avoid denaturation and loss of structure, measured as melting temperature (T).

CollagenTransformer: End-to-End Transformer Model to Predict Thermal Stability of Collagen Triple Helices Using an NLP Approach.

Collagen is one of the most important structural proteins in biology, and its structural hierarchy plays a crucial role in many mechanically important biomaterials. Here, we demonstrate how transformer models can be used to predict, directly from the primary amino acid sequence, the thermal stability of collagen triple helices, measured via the melting temperature . We report two distinct transformer architectures to compare performance.

3D Printing of Monolithic Proteinaceous Cantilevers Using Regenerated Silk Fibroin.

Silk fibroin, regenerated from , has shown considerable promise as a printable, aqueous-based ink using a bioinspired salt-bath system in our previous work. Here, we further developed and characterized silk fibroin inks that exhibit concentration-dependent fluorescence spectra at the molecular level. These insights supported extrusion-based 3D printing using concentrated silk fibroin solutions as printing inks.

Charge-Modulated Accessibility of Tyrosine Residues for Silk-Elastin Copolymer Cross-Linking.

The modulation of reaction kinetics with horseradish peroxidase (HRP)-catalyzed cross-linking of proteins remains a useful strategy to modulate hydrogel formation. Here, we demonstrate that the presence of positively charged lysines in silk-elastin-like polymers impacts the thermal transition temperature of these proteins, while the location in the primary sequence modulates the reactivity of the tyrosines. The positively charged lysine side chains decreased π-π interactions among the tyrosines and reduced the rate of formation and number of HRP-mediated dityrosine bonds, dependent on the proximity of the charged group to the tyrosine.

Fast and reversible crosslinking of a silk elastin-like polymer.

Elastin-like polymers (ELPs) and their chimeric subfamily the silk elastin-like polymers (SELPs) exhibit a lower critical solvation temperature (LCST) behavior in water which has been extensively studied from theoretical, computational and experimental perspectives. The inclusion of silk domains in the backbone of the ELPs effects the molecular dynamics of the elastin-like domains in response to increased temperature above its transition temperature and confers gelation ability. This response has been studied in terms of initial and long-term changes in structures, however, intermediate transition states have been less investigated.

Complex Morphogenesis by a Model Intrinsically Disordered Protein.

The development of intricate and complex self-assembling structures in the micrometer range, such as biomorphs, is a major challenge in materials science. Although complex structures can be obtained from self-assembling materials as they segregate from solution, their size is usually in the nanometer range or requires accessory techniques. Previous studies with intrinsically disordered proteins (IDPs) have shown that the active interplay of different molecular interactions provides access to new and more complex nanostructures.

A transferrin receptor-binding mucoadhesive elastin-like recombinamer: In vitro and in vivo characterization.

The development of mucoadhesive materials is of great interest and is also a major challenge. Being adsorption sites, mucosae are suitable targets for drug delivery, but as defensive barriers they are complex biological surfaces to interact with, mainly due to their protective mucus layer. As such, first- and second-generation mucoadhesives focused on material-mucus interactions, whereas the third generation of mucoadhesives introduced structural motifs that are able to interact with the cells beneath the mucus layer.

Recombinant Technology in the Development of Materials and Systems for Soft-Tissue Repair.

The field of biomedicine is constantly investing significant research efforts in order to gain a more in-depth understanding of the mechanisms that govern the function of body compartments and to develop creative solutions for the repair and regeneration of damaged tissues. The main overall goal is to develop relatively simple systems that are able to mimic naturally occurring constructs and can therefore be used in regenerative medicine. Recombinant technology, which is widely used to obtain new tailored synthetic genes that express polymeric protein-based structures, now offers a broad range of advantages for that purpose by permitting the tuning of biological and mechanical properties depending on the intended application while simultaneously ensuring adequate biocompatibility and biodegradability of the scaffold formed by the polymers.