Complex Morphogenesis out of Self-Organizing Polypeptide Recombinamers with High Intrinsic Disorder—From Bioinks to Biomorphs

Natural structures are the result of complex hierarchical self-assembling processes. The complexity in those arrives from many fronts. First, the self-assembling molecules are already very complex in composition. Second, most, if not all, the organized structures correspond to far-from-equilibrium states. Third, in many cases they involve the concurrent self-assembling processes of different macromolecules. Fourth, dynamic interactions, environmental responsiveness and adaptability are common properties in those systems. In addition to all that, self-assembly of biological molecules seems to be the result of an order-disorder interplay in which intrinsically disordered molecules, or notable domains in them, play an essential role. Therefore, if one wants to understand and mimic such extraordinary processes, it is necessary to design model systems in which complexity, intrinsic disorder, dynamic behavior, and far-from-equilibrium states are preeminent. This draws a totally different paradigm to the one existing for the more conventional approach in designing most of the present self-assembling systems.<br/>Recombinant technology is a powerful tool to fabricate such complex, but well-defined, and multifunctional macromolecules. Its polypeptide nature permits to include in their molecular design any peptide domain existing on natural proteins that can be of interest. On the other hand, as recombinamers are based in a totally synthetic DNA, the combination of peptide domains is essentially not restricted by any factor and, practically any composition of interest can be produced. Those may include even peptide domains that are not found in natural prote ins but they could be of interest.<br/>During those last years, different recombinamers have been designed and tested in our lab. Some of the molecular designs have proven to be, for example excellent 3D bioinks [1]. In those, superior printability is obtained by an adequate programing, at molecular level, of a sequence of self-organizing events with different strengths and dynamics while showing excellent bioactivity and biocompatibility. In other cases, the combination of competing and independent self-organizing interactions some of them generating out of equilibrium stable arrangements has lead to the generation of complex 3D structures after a process of spinodal decomposition of T-sensitive high MW recombinamers with LCST behavior.<br/><b>References</b><br/>[1]. Soraya Salinas-Fernández, Mercedes Santos, Matilde Alonso, Luis Quintanilla, José Carlos Rodríguez-Cabello. Genetically engineered elastin-like recombinamers with sequence-based molecular stabilization as advanced bioinks for 3D bioprinting. Applied Materials Today. Volume 18, March 2020, 100500<br/>[2]. Constancio González-Obeso, Miguel González-Pérez, João F. Mano, Matilde Alonso, José Carlos Rodríguez-Cabello. Complex Morphogenesis by a Model Intrinsically Disordered Protein. Small 2020, 16, 2005191