Evaluation of Potential of Zwitterionic Salts for the Development of Protein-Resistant Surfaces

Unwanted protein adsorption on medical devices can cause numerous problems such as blood coagulation, inflammation, thrombosis, failure of implants, malfunctioning of biosensors and drug delivery systems, and loss of activity of therapeutically formulated protein solutions. Protein fouling on biotechnological equipment can cause reduced flux through membranes, blocking of separating columns and loss of valuable biomaterials. Since unwanted protein adsorption is a global problem faced by many industries, a lot of efforts have been made to find efficient technology for supressing attachment of proteins on various type of surfaces (metal, polymer, ceramic, silicone). Commonly considered approaches to prevent protein adsorption are based on modification of surfaces of interest by applying coatings formed by self-assembled monolayers (SAMs), grafted polymer layers, and polymer brushes. The coatings support specific functional groups (as zwitterion, hydroxyl) which control surface charge, wettability, hydrophobicity, free energy, and interaction with biomolecules.
The proposed research will evaluate the potential of zwitterionic salt (ZWS)-functionalised coatings and test their potential to suppress protein attachment. ZWSs are a novel class of molecules that combine properties of inorganic salts, ionic liquids and common two-charge zwitterions. ZWSs offer the possibility of functionalization of cation and anion or for use as functional groups attached on long alkyl chains or polymers, and supported on a substrate. They possess four charge centres in their molecules and increased charged surface area leading to strong hydration, as experimentally confirmed. The fact that key underling phenomenon of surface resistance to non-specific protein adsorption is its strong hydration clearly indicates the potential of ZWSs in the proposed application. The project aims to provide understanding at a fundamental level of the interactions between ZWSs, water and proteins through the a range of analytical techniques and scientific methods. These interactions will be reflected in the performances of zwitterionic salt (ZWS)-functionalised coatings, but they will also guide future research strategies and applications.

A common problem with implantable medical devices is undesirable protein adsorption which can cause inflammation, fibrosis, and infection, thus, causing enormous discomfort to patients and high cost to NHS. The proposal has an explicit long-term goal to develop and commercialise protein-resistant surfaces. Development of coatings that can reduce protein adsorption, if supported by companies (e.g. Abbott UK), would deliver advances to healthcare system and put UK in a leading position in manufacturing in this area. General public and patients would benefit in a great extent, since the advanced medical devices could improve patient's recovery and quality of life.
Since high hydrophilicity is an important requirement in various biotechnological and chemical processes, it is expected that both economic and academic beneficiaries will be extended far beyond the immediate project aims. The potential applications might use ZWSs as additives, main components in mixtures or functional groups supported on substrates.
However, the project will initially be focused on fundamental research which should enhance the understanding of characteristics of zwitterionic salts as functional groups and they effects on both chemistry in solutions and surface chemistry. This is a pioneering work aiming to bring an insight on properties of ZWSs, and their interactions with water and proteins; these findings can be important for many different scientific disciplines and have diverse practical implications.
Working on the project, a PDRA and students (one PhD and two MEng students) will benefit through learning many experimental techniques, developing expertise in project management, improving communication skills and experience in outreach activities, and engagement with media and public. These acquired skills will improve their employability in both academia and industry as highly qualified workers.
The project would help MB to consolidate a successful research group and extend her network of collaborators. It is expected that collaborative work and joint expertise will enhance knowledge transfer between institutions on both national and international level, and result in high quality publications. It will help MB to support her applications for future funding.