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Amphiphilic Elastin-Like Block Co-Recombinamers Containing 2 Leucine Zippers: Cooperative Interplay between Both Domains 3 Results in Injectable and Stable Hydrogels
Año del Documento
Biomacromolecules. 2015 Oct 12;16(10):3389-98
Many biological processes are regulated by reversible binding events, with these interactions between macromolecules representing the core of dynamic chemistry. As such, any attempt to gain a better understanding of such interactions, which would pave the way to the extrapolation of natural designs to create new advanced systems, is clearly of interest. This work focuses on the development of a leucine zipper-elastin-like recombinamer (ZELR) in order to elucidate the behavior of such domains when coexisting along the same molecule and to engineer reversible, injectable and stable hydrogels. The unique propensity of the Z-moiety selected to dimerize, together with the thermosensitive behavior of the ELR, which has been constructed as a thermosensitive amphiphilic tetrablock, has been engineered into a single recombinant molecule. In this molecular design, the Z-moieties are unable to form a network, while the ELR is below its Tt, thus, guaranteeing the liquid-like state of the system. However, this situation changes rapidly as the temperature increases above Tt, where a stable hydrogel is formed, as demostrated by rheological tests. The inability of the ELR molecule (without Z-domains) to form such a stable hydrogel above Tt clearly points to a positive cooperative effect between these two domains (Z and EL), and no conformational changes in the former are involved, as demonstrated by circular dichroism analysis. AFM shows that Z-motifs seem to induce the aggregation of micelles, which supports the enhanced stability displayed by ZELRs when compared to ELR at the macroscale level. To the best of our knowledge, this is the first time that such an interplay between these two domains has been reported. Furthermore, the cytocompatibility of the resulting hydrogels opens the door to their use in biomedical applications.
Revisión por pares
Este trabajo forma parte de Proyectos de Investigación financiados por la Comisión Europea a través del Fondo Social Europeo (FSE) y el Fondo Europeo de Desarrollo Regional (ERDF), por el del MINECO (MAT2013-41723R, MAT2013-42473-R, MAT2012-38043 y PRI-PIBAR-2011-1403), la Junta de Castilla y León (VA049A11, VA152A12 y VA155A12) y el Instituto de Salud Carlos III bajo el Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León.