RESUMO
Nanoscopic structural control with long-range ordering remains a profound challenge in nanomaterial fabrication. The nanoarchitectured egg cases of elasmobranchs rely on a hierarchically ordered latticework for their protective functionâserving as an exemplary system for nanoscale self-assembly. Although the proteinaceous precursors are known to undergo intermediate liquid crystalline phase transitions before being structurally arrested in the final nanolattice architecture, their sequences have so far remained unknown. By leveraging RNA-seq and proteomic techniques, we identified a cohort of nanolattice-forming proteins comprising a collagenous midblock flanked by domains typically associated with innate immunity and network-forming collagens. Structurally homologous proteins were found in the genomes of other egg-case-producing cartilaginous fishes, suggesting a conserved molecular self-assembly strategy. The identity and stabilizing role of cross-links were subsequently elucidated using mass spectrometry and in situ small-angle X-ray scattering. Our findings provide a new design approach for protein-based liquid crystalline elastomers and the self-assembly of nanolattices.
Assuntos
Cristais Líquidos , Tubarões , Animais , Colágeno , Humanos , Cristais Líquidos/química , Transição de Fase , ProteômicaRESUMO
Structural versatility and multifunctionality of biological materials have resulted in countless bioinspired strategies seeking to emulate the properties of nature. The nanostructured egg case of swell sharks is one of the toughest permeable membranes known and, thus, presents itself as a model system for materials where the conflicting properties, strength and porosity, are desirable. The egg case possesses an intricately ordered structure that is designed to protect delicate embryos from the external environment while enabling respiratory and metabolic exchange, achieving a tactical balance between conflicting properties. Herein, structural analyses revealed an enabling nanolattice architecture that constitutes a Bouligand-like nanoribbon hierarchical assembly. Three distinct hierarchical architectural adaptations enhance egg case survival: Bouligand-like organization for in-plane isotropic reinforcement, noncylindrical nanoribbons maximizing interfacial stress distribution, and highly ordered nanolattices enabling permeability and lattice-governed toughening mechanisms. These discoveries provide fundamental insights for the improvement of multifunctional membranes, fiber-reinforced soft composites, and mechanical metamaterials.
Assuntos
Nanoestruturas , Tubarões , Animais , Permeabilidade , PorosidadeRESUMO
Despite the advanced detection and sterilization techniques available today, the sensitive diagnosis and complete elimination of bacterial infections remain a significant challenge. A strategy is reported for efficient bacterial capture (ca. 90%) based on the synergistic effect of the nanotopography and surface chemistry of the substrate on bacterial attachment and adhesion. The outstanding bacterial-capture capability of the functionalized nanostructured substrate enables rapid and highly sensitive bacterial detection down to trace concentrations of pathogenic bacteria (10â colony-forming units mL(-1)). In addition, this synergistic biocapture substrate can be used for efficient bacterial elimination and shows great potential for clinical antibacterial applications.
Assuntos
Bactérias/metabolismo , Nanotecnologia/métodos , Sinergismo Farmacológico , Humanos , NanoestruturasRESUMO
In recent years, multidrug therapy has gained increasing popularity due to the possibility of achieving synergistic drug action and sequential delivery of different medical payloads for enhanced treatment efficacy. While a number of composite material release platforms have been developed, few combine the bottom-up design versatility of metal-organic frameworks (MOFs) to tailor drug release behavior, with the convenience of temperature-responsive hydrogels (or thermogels) in their unique ease of administration and formulation. Yet, despite their potential, MOF-thermogel composites have been largely overlooked for simultaneous multidrug delivery. Herein, we report the first systematic study of common MOFs (UiO-66, MIL-53(Al), MIL-100(Fe), and MOF-808) with different pore sizes, geometries, and hydrophobicities for their ability to achieve simultaneous dual drug release when embedded within PEG-containing thermogel matrices. After establishing that MOFs exert small influences on the rheological properties of the thermogels despite the penetration of polymers into the MOF pores in solution, the release profiles of ibuprofen and caffeine as model hydrophobic and hydrophilic drugs, respectively, from MOF-thermogel composites were investigated. Through these studies, we elucidated the important role of hydrophobic matching between MOF pores and loaded drugs in order for the MOF component to distinctly influence drug release kinetics. These findings enabled us to identify a viable MOF-thermogel composite containing UiO-66 that showed vastly different release kinetics between ibuprofen and caffeine, enabling temporally differentiated yet sustained simultaneous drug release to be achieved. Finally, the MOF-thermogel composites were shown to be noncytotoxic in vitro, paving the way for these underexploited composite materials to find possible clinical applications for multidrug therapy.
Assuntos
Cafeína , Ibuprofeno , Quimioterapia Combinada , HansenostáticosRESUMO
Thermogels, a class of hydrogels which show spontaneous sol-gel phase transition when warmed, are an important class of soft biomaterials. To date, however, most amphiphilic polymers that are able to form thermogels in aqueous solution are uncharged, and the influence of ionisable groups on thermogelation are largely unknown. Herein, we report the first example of a polyanionic amphiphilic multi-block copolymer, containing multiple pendant carboxylate groups, that can form transparent thermogels spontaneously when warmed up to physiological temperature. We demonstrate that introducing negative charges onto thermogelling polymers could significantly alter the properties of the micelles and thermogels formed. Furthermore, the polymer's polyanionic character provides new options for modulating the gel rheological properties, such as stiffness and gelation temperatures, through electrostatic interactions with different cations. We also demonstrated that the polyanionic thermogel allowed slower sustained release of a cationic model drug compound compared to an anionic one over 2â weeks. The findings from our study demonstrate exciting new possibilities for advanced biomedical applications using charged polyelectrolyte thermogel materials.
Assuntos
Hidrogéis , Tartaratos , Temperatura , Polieletrólitos , PolímerosRESUMO
Suckerin proteins are a family of block co-polymer-like structural proteins that self-assemble into robust supramolecular structures - the sucker ring teeth (SRT) - which are located on the arms and tentacles of cephalopods and used to firmly capture preys. Suckerins are promising biomimetic protein-based biopolymers, but the supramolecular interactions stabilizing SRT remain unknown. Here, we report multi-dimensional Nuclear Magnetic Resonance (NMR) spectroscopy structural studies of an engineered suckerin protein composed of two main sequence modules. The protein adopts a dynamic structure with regions in both module 1 (M1: residues A42-A52) and module 2 (M2: residues G30-Y37 and G58-Y65) folding into anti-parallel ß-sheets and displaying ß-strand propensity, respectively. The obtained structure highlights that aromatic residues present in glycine (Gly)-rich M2 modules are involved in π-π stacking interactions, leading to the stabilization of the structural core. In addition, hydrogen/deuterium (H/D) exchange studies demonstrate a high protection of residues involved in intra-molecular ß-sheets. Gaining a better understanding of the molecular structure of suckerin provides key molecular lessons that may be mimicked in the de novo design of peptide- and protein-based biomaterials with applications in medicine, tissue engineering and nanotechnology.