Peptide metal-organic frameworks under pressure: flexible linkers for cooperative compression

We investigate the structural response of a dense peptide metal-organic framework using in situ powder and single-crystal X-ray diffraction under high-pressures. Crystals of Zn(GlyTyr)2 show a reversible compression by 13% in volume at 4 GPa that is facilitated by the ability of the peptidic linker to act as a flexible string for a cooperative response of the structure to strain. This structural transformation is controlled by changes to the conformation of the peptide, which enables a bond rearrangement in the coordination sphere of the metal and changes to the strength and directionality of the supramolecular interactions specific to the side chain groups in the dipeptide sequence. Compared to other structural transformations in Zn(II) peptide MOFs, this behaviour is not affected by host/guest interactions and relies exclusively on the conformational flexibility of the peptide and its side chain chemistry

Development of a framework for designing nucleic acid-based, out-of-equilibrium catalytic reaction networks.

DNA nanotechnology and Toehold Mediated Strand Displacement (TMSD) offer the possibility of building systems that display complex algorithmic behaviours. However, up to the present point most systems based in this technology act as one-shot systems that relax into equilibrium when they operate and lose any chance of responsiveness and adaptation to changing environmental outputs. This situation is starkly opposed to how living systems react to changes in their environment and implement finely-tuned responses. Cells perform this feat via biochemical transduction networks, which have previously been described as distributed computational systems operating out of thermodynamic equilibrium. While transduction networks are highly complex, their fundamental building motif is well known: the push-pull network. In this motif, a substrate is switched between two states via two fuel-consuming catalysts. This out-of-equilibrium operation allows push-pull systems to propagate information robustly in signal-transduction cascades presenting while complex dynamics. Understanding the main operational constraints of push-pull systems is a fundamental question in systems biology and a requirement for their proper use in synthetic biology. Moreover, building DNA-based analogues of push-pull systems would allow us to explore these fundamental questions and provides an ideal engineering platform for implementing non-equilibrium information processing systems in biological and nanotechnology contexts. While emulating the behaviour of transduction network in TMSD systems is possible in principle, there are several performance issues that hinder this possibility. In order to overcome these limitations, we propose the Active Circuits of Duplex Catalysts (ACDC) Framework to meet this challenge. In ACDC, all species are DNA duplexes that interact directly via four-way strand exchange. The present thesis demonstrates that the ACDC Framework can successfully implement all the prerequisite to build extended catalytic reaction networks. Additionally, we discuss functional and formal limitations of the Framework as well as the role of thermodynamic drives in overcoming them.Open Acces

Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration

[EN] Hyaluronan-based hydrogels are among the most promising neural tissue engineering materials because of their biocompatibility and the immunomodulation capabilities of their degradation byproducts. Despite these features, the problems related to their handling and mechanical properties have not yet been solved. In the present work it is proposed to address these drawbacks through the development of nanohybrid materials in which different nanometric phases (carbon nanotubes, mesoporous silica nanoparticles) are embedded in a crosslinked hyaluronan matrix. These nanohybrid matrices were next processed in the shape of cylindrical conduits aimed at promoting and improving neural stem cell differentiation and regeneration in neural tracts. These constructs could be of use specifically for peripheral nerve regeneration. Results of the study show that the inclusion of the different phases improved physico-chemical features of the gel such as its relative electrical permittivity, water intake and elastic modulus, giving hints on how the nanometric phase interacts with hyaluronan in the composite as well as for their potential in combined therapeutic approaches. Regarding the in vitro biological behavior of the hybrid tubular scaffolds, an improved early cell adhesion and survival of Schwann cells in their lumen was found, as compared to conduits made of pure hyaluronan gels. Furthermore, the differentiation and survival of neural precursors was not compromised, despite alleged safety concerns.The authors acknowledge funding through the MAT2011-28791-C03-02,03 project from the Spanish Ministerio de Economia y Competitividad. The authors thank deeply the advice of C. Martinez Ramos, Ph.D. on the cell culture tasks, Prof. J. M. Meseguer Duenas on the dielectric impedance spectroscopy, and S. Ivaschenko with FTIR spectroscopy. Lastly, Prof. P. Amoros from Institut de Ciencia de Materials of Universitat de Valencia (ICMUV) and Prof. J. M. Verdugo are thanked for providing the mesoporous silica nanoparticles and the rat neurospheres, respectively. The Electronic Microscopy Service of the Universitat Politecnica de Valencia is acknowledged their help and dedication.Mullor Ruiz, I.; Vilariño-Feltrer, G.; Mnatsakanyan, H.; Vallés Lluch, A.; Monleón Pradas, M. (2021). Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration. Journal of Biomaterials Science Polymer Edition. 32(17):2227-2245. https://doi.org/10.1080/09205063.2021.1963930S22272245321