RESUMO
Peptide-based hydrogels are promising biocompatible materials for wound healing, drug delivery, and tissue engineering applications. The physical properties of these nanostructured materials depend strongly on the morphology of the gel network. However, the self-assembly mechanism of the peptides that leads to a distinct network morphology is still a subject of ongoing debate, since complete assembly pathways have not yet been resolved. To unravel the dynamics of the hierarchical self-assembly process of the model ß-sheet forming peptide KFE8 (Ac-FKFEFKFE-NH2 ), high-speed atomic force microscopy (HS-AFM) in liquid is used. It is demonstrated that a fast-growing network, based on small fibrillar aggregates, is formed at a solid-liquid interface, while in bulk solution, a distinct, more prolonged nanotube network emerges from intermediate helical ribbons. Moreover, the transformation between these morphologies has been visualized. It is expected that this new in situ and in real-time methodology will set the path for the in-depth unravelling of the dynamics of other peptide-based self-assembled soft materials, as well as gaining advanced insights into the formation of fibers involved in protein misfolding diseases.
Assuntos
Nanoestruturas , Peptídeos , Conformação Proteica em Folha beta , Peptídeos/química , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , Microscopia de Força AtômicaRESUMO
Non-covalent π-π stacking interactions often play a key role in the stability of the secondary and tertiary structures of peptides and proteins, respectively, and can be a means of ensuring the binding of ligands within protein and enzyme binding sites. It is generally accepted that minor structural changes to the aromatic ring, such as substitution, can have a large influence on these interactions. Nevertheless, a thorough understanding of underpinning phenomena guiding these key interactions is still limited. This is especially true for larger aromatic structures. To expand upon this knowledge, elaborate ab initio calculations were performed to investigate the effect of halogenation on the stability of 3-methylindole stacking. 3-Methylindole served as a representation of the tryptophan side chain, and is a frequently used motif in drug design and development. Moreover, an expression is derived that is able to accurately predict the interaction stability of stacked halogenated 3-methylindole dimers as well as halogenated toluene dimers, based on monomer level calculated DFT descriptors. We aim for this expression to provide the field with a straightforward and reliable method to assess the effect of halogenation on the π-π stacking interactions between aromatic scaffolds.
RESUMO
Two reversible polymer networks, based on Diels-Alder cycloadditions, are selected to discuss the opportunities of mobility-controlled self-healing in ambient conditions for which information is lacking in literature. The main methods for this study are (modulated temperature) differential scanning calorimetry, microcalorimetry, dynamic rheometry, dynamic mechanical analysis, and kinetic simulations. The reversible network 3M-3F630 is chosen to study the conceptual aspects of diffusion-controlled Diels-Alder reactions from 20 to 65 °C. Network formation by gelation is proven and above 30 °C gelled glasses are formed, while cure below 30 °C gives ungelled glasses. The slow progress of Diels-Alder reactions in mobility-restricted conditions is proven by the further increase of the system's glass transition temperature by 24 °C beyond the cure temperature of 20 °C. These findings are employed in the reversible network 3M-F375PMA, which is UV-polymerized, starting from a Diels-Alder methacrylate pre-polymer. Self-healing of microcracks in diffusion-controlled conditions is demonstrated at 20 °C. De-gelation measurements show the structural integrity of both networks up to at least 150 °C. Moreover, mechanical robustness in 3M-F375PMA is maintained by the poly(methacrylate) chains to at least 120 °C. The self-healing capacity is simulated in an ambient temperature window between -40 and 85 °C, supporting its applicability as self-healing encapsulant in photovoltaics.