General Overview of our Research

Proteins as building blocks for nanofabrication and biomaterials

Proteins are the most versatile biological building blocks, composed of amino acids offering rich chemistry. Proteins present enormous diversity in 3D structures that translates into amazing functional diversity. Thus proteins have great potential for use as building blocks in order to construct tailored designed systems, including nanofabrication and generation of novel protein-based biomaterials. Our group explores the potential of proteins as building blocks toward the generation of functional nanostructures and bioinspired materials for applications in nanobiotechnology and nanomedicine. In particular, our main objective is to develop versatile platforms based on simple protein building blocks for the fabrication of multiple protein-based hybrid functional nanostructures and biomaterials.

Key references:

Self-assembly of repeat proteins: Concepts and design of new interfaces
D. Sanchez-de Alcazar, S. H. Mejias, K. Erazo, B. Sot, A. L. Cortajarena.
J. Struct. Biol. 2018, in press.

Biomolecular templating of functional hybrid nanostructures using repeat protein scaffolds
D. Romera, P. Couleaud, S. H. Mejias, A. Aires, A. L. Cortajarena.
Biochem. Soc. Trans. 2015, 43, 825-831.

Controlled nanometric fibers of self-assembled designed protein scaffolds
S. H. Mejias, B. Sot, R. Guantes, A. L. Cortajarena.
Nanoscale 2014, 6, 10982-10988.

Proteins to template nanomaterials

Designed proteins provide us the ability to finely control the patterning of elements such as gold nanoparticles and gold nanorods at the nanoscale in order to form supramolecular structures with desired properties. Our goal is to demonstrate that the use of proteins to template nanomaterials not only provides control over the systems arrangement at the nanometer scale, but also confers new properties to the nanomaterials, such as chirality, with interesting applications in nanoelectronics and bioplasmonics among others.

Key reference:

Assembly of designed protein scaffolds into monolayers for nanoparticle patterning
S. H. Mejias, P. Couleaud, S. Casado, D. Granados, M. A. Garcia, J. M. Abad, A. L. Cortajarena.
Colloids Surf. B Biointerfaces 2016, 141, 93-101.

Design proteins for biomolecular electronics

The precise control over the organisation of photo and electro active components at the nanoscale is one of the main challenges for the development of the new generation of bioinspired systems and their application in “biomolecular electronics”. We exploit the potential of proteins as biomolecular scaffolds to template complex photoactive and electroactive systems. We aim to construct efficient light harvesting antennas and energy transductors.

Key references:

Toward bioelectronic nanomaterials: Photoconductivity in Protein-Porphyrin Hybrids Wrapped around SWCNT
J. López-Andarias, S.H. Mejías, T. Sakurai, W. Matsuda, S. Seki, F. Feixas, S. Osuna, C. Atienza, N. Martín, A. L. Cortajarena.
Adv. Funct. Mat. 2017, DOI: 10.1002/adfm.201704031.

Repeat protein scaffolds: Ordering photo- and electroactive molecules in solution and solid state
S. H. Mejías, J. López-Andarias, T. Sakurai, S. Yoneda, K. P. Erazo, S. Seki, C. Atienza, N. Martín, A. L. Cortajarena.
Chem. Sci. 2016, 7, 4842-4847.

Designed protein scaffolds to stabilise metal nanoclusters

Metal nanoclusters exhibit very interesting optical, electronical and chemical properties, including strong photoluminescence, excellent photostability and good biocompatibility, while being sub-nanometer in size. Such properties make metal NCs ideal nanomaterials for applications in biological analysis and imaging, environmental monitoring, industrial catalysis and photoelectronic devices. In this project, we explore the potential of designed repeat proteins as templates for the synthesis and stabilization of metal nanoclusters and their biological application in sensing and imaging.


Key reference:

Designed modular proteins as scaffolds to stabilize fluorescent nanoclusters
P. Couleaud, S. Adan-bermudez, A. Aires, S. H. Mejias, B. Sot, A. Somoza, A. L. Cortajarena.
Biomacromolecules 2015, 16, 3836-3844.

Designed proteins for biocatalysis

De novo design of proteins whose both structure and function are built from first principles represents a considerable challenge. Artificial proteins-like catalysts constructed in this way would be of great interest for the synthesis and/or modification of small molecules with potential applications in biotechnology and medicine. It is possible to generate protein folds that in their nature are not related to biological catalysts in order to emulate inorganic and/or organic catalysts through design and engineering. In this project, we work towards the design of repeat protein scaffolds as biocatalysts to facilitate reactions not performed by any currently described proteins.

Protein-based biomaterials

Nanostructured protein films can be fabricated using repeat protein modules, through intrinsic head-to-tail and side-to-side interactions. The materials show order from the nanometric to the macroscopic scale. One advantage of using these repeated modules for the generation of highly ordered materials is the ability of the proteins maintain their structure in the solid state. Therefore, the structural information of the units from their crystal structure can be applied to the solid films in order to generate materials with functionalities arranged at defined positions. We explore the potential of repeated building blocks in the design of functional hybrid biomaterials using bottom-up rational approaches.

Key references:

Designed Repeat Proteins as Building Blocks for Nanofabrication
S. H. Mejias, A. Aires, P. Couleaud, A. L. Cortajarena.
Adv. Exp. Med. Biol. 2016, 940, 61-81.

Nanostructured films from engineered repeat proteins
T. Z. Grove, L. Regan, A. L. Cortajarena.
J. R. Soc. Interfase 2013, 10, 20130051.

Biofunctionalisation of nanomaterials: nanomedicine

Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. We develop new methodologies for the generation of versatile functional nanoparticles for biomedical applications from disease treatment to imaging. We pay special attention to functionalisation with biomolecules and to the generation of final formulations with optimal properties, including their biocompatibility and stability, selective drug release and targeting capabilities, for being used under clinically relevant conditions. For this aim, we study the fundamental aspects that govern the fate and efficiency of the nanoformulations, including their physico-chemical properties. We combine systematic experimental approaches and simulations. Our work is focussed on providing new guidelines to guide the rational design of efficient and selective nanomedicines.

Key references:

An experimental and computational framework for engineering multifunctional nanoparticles: designing selective anticancer therapies
A. Aires, J. F. Cadenas, R. Guantes, A. L. Cortajarena.
Nanoscale 2017, 9, 13760-13771.

Elucidation of the Physicochemical Properties Ruling the Colloidal Stability of Iron Oxide Nanoparticles under Physiological Conditions
A. Aires, D. Cabrera, L. C. Alonso-Pardo, A. L. Cortajarena*, F. J. Teran*.
ChemNanoMat 2017, 3, 183-189.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death
A. I. Martínez-Banderas, A. Aires, F. J. Teran, J. E. Perez, J. F. Cadenas, N. Alsharif, T. Ravasi, A. L. Cortajarena, J. Kosel.
Sci. Rep. 2016, 6, 35786.

BSA-coated magnetic nanoparticles for improved therapeutic properties
A. Aires, S. M.Ocampo, D. Cabrera, L. de la Cueva, G. Salas, F. J. Teran, A. L. Cortajarena.
J. Mater. Chem. B 2015, 3, 6239-6247.

Functional polymeric materials

We work on the design and characterisation of polymeric materials and surfaces. In this sense, combining the structural patterning with the functionalisation of polymeric surfaces using biomolecules, we design platforms with defined properties for biorecognition, bacterial-templating and bactericidal activity. We evaluate the biological activity of these advanced materials and surfaces.

Key references:

Antimicrobial 3D Porous Scaffolds Prepared by Additive Manufacturing and Breath Figures
N. Vargas-Alfredo, A. Dorronsoro, A. L. Cortajarena, J. Rodríguez-Hernández.
ACS Appl. Mater. Interfaces 2017, 9, 37454–37462.

Hydrogels with Modulated Ionic Load for Mammalian Cell Harvesting with Reduced Bacterial Adhesion
A. Gallardo, E. Martínez-Campos, C. García, A. L. Cortajarena, J. Rodríguez-Hernández.
Biomacromolecules 2017, 18, 1521-1531.

Honeycomb patterned surfaces functionalized with polypeptide sequences for recognition and selective bacterial adhesion
A. Sanz de León, J. Rodríguez-Hernández, A. L. Cortajarena.
Biomaterials 2013, 34, 1453-1460.

Preparation of Biodegradable Cationic Polycarbonates and Hydrogels Through the Direct Polymerization of Quaternized Cyclic Carbonates
A. Y. Yuen, E. Lopez-Martinez, E. Gomez-Bengoa, A. L. Cortajarena, R. H. Aguirresarobe, A. Bossion, D. Mecerreyes, J. L. Hedrick, Y. Y. Yang, H. Sardon.
ACS Biomater. Sci. Eng. 2017, 3, 1567-1575.

Funding

Our research is made possible by these organisations: