The goal of this project is to develop part of the activities included in the proposal ARIBA (Advanced Responsive Interfaces for Biological Applications) submitted under the H2020-MSCA-ITN scheme in 2014. The original proposal was aimed at developing a training network across Europe to research responsive interfaces for biomaterial and biotechnology related applications, with potential application areas in biomolecule encapsulation and release, anti-biofouling surfaces, 3D cell culture, and pharmaceutical testing. In particular, we will focus on one of the research goals of ARIBA, which was to design and create novel functionalized material interfaces that can be controlled by external stimuli so to induce a biological response defined in space and time. The specific areas that will be researched are the grafting of novel responsive polymer brushes to create responsive patterns and gradients, which can (i) rapidly respond, (ii) be multi-responsive, and (iii) preferably be controlled by externally applied electromagnetic fields. Particular focus will be on biointerfaces which can be externally controlled to change the release of drugs or cell adhesion.
The project brings together expertise from highly experienced researchers at Sapienza University and international collaborators in synthesis and characterization of polymer brushes for biological applications (e.g. membrane protein arrays and sensors), processing of polymer materials and polymer-matrix composites with multifunctional properties. Our ultimate goal is to demonstrate how these versatile interfaces engineered to include responsive functions can be used to control the integration of a material with biomolecules in space and time. The project includes training for two doctoral students who will experience the complementarity of several disciplines, from biointerface science to composite materials processing, and will participate in research activities at international partners.
Biological systems are very sensitive to their environment. Environmental cues such as biochemical recognition sites, spacing and distribution of recognition groups, mechanical stiffness, fluidity, shape, biochemical and chemical gradients have all been implicated to influence biological response, migration and differentiation of cells and tissue. Our understanding of the extent of these influences, how to deconvolute them and how to apply them in order to achieve predictable biological responses in diverse applications is still fragmentary; accordingly, this is a subject of substantial research effort. Very basic functions such as mobility, temporal and environmental adaptability are mostly missing. Gradients in function and the hierarchical structuring of physicochemical properties over many length and force scales are still mainly visions tested in the laboratory.
Our ultimate goal is to demonstrate how interfaces engineered to include a responsive function can be used to control the integration of a material with a biological system. Traditional interfaces developed for commercial biomedical applications can at best be considered functional, but are generally passive. From a set of given properties defined at the outset they will induce a certain set of responses in the biological system they contact. The repertoire of responses has been limited by the simplicity of the biomaterial¿s composition, e.g., glass, titania, or polystyrene, which is occasionally chemically modified to promote a desired biological interaction. To address these shortcomings, technologies have focused on utilizing a more versatile and biomimetic approach to modify cell and biomolecule interacting interfaces with highly hydrated and flexible polymers (Falconnet et al, Biomaterials, 2006; Mendes, Chemical Society Reviews, 2008), or with biomolecules such as peptides, proteins and lipids (Mossman et al, Science, 2005; Andreasson-Ochsner et al, Lab on a Chip, 2011; Nath et al, Advanced Materials, 2012). However, even in this more advanced approach, the substrate properties remain unchanged over time and can induce only one immutable cellular response with no possibility of response modulation and adaptation to an evolving biological environment. There is an urgent need to improve upon this rudimentary control, and to create artificial interfaces that just like their biological counterparts are inherently adaptable to changing conditions or under external control can change their physicochemical properties at the molecular level in a time-dependent, programmable manner. The originality of our research program lies in the investigation and application of three concepts:
1. Long- range and externally rearrangeable molecular interfaces
2. Strong and specific interactions through multivalency enabled by fluid interfaces
These concepts will be tailored to specific applications. One of this will be the development of innovative cell culture platforms for use in drug discovery and tissue engineering, or for biosensor targeting pharmaceutically-relevant proteins, such as membrane proteins.