Folded protein hydrogel characterisation

Folded protein hydrogels consist of protein domains crosslinked together, forming a network. These responsive, functional materials exploit the protein's mechanics and biological function. The application of force can break secondary intramolecular bonds and interactions, leading to protein unfolding. Control of protein unfolding during network formation enables the design of biomaterials with distinct architecture and mechanical properties with application for example, as drug delivery systems. Hydrogel structures and mechanics have been characterised through a multiscale approach involving atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and rheology. They have a heterogeneous structure consisting of areas with folded protein clusters connected by areas of unfolded protein. Small angle scattering techniques require fitting models to reciprocal or scattering (Q-)space data providing indirect measures. Electron microscopy (EM) techniques could provide direct imaging of these structures. However, dehydration under the high vacuum conditions required for EM must be avoided by keeping the hydrated sample frozen (cryo-EM). For this purpose, a bovine serum albumin (BSA) hydrogel was prepared to initially image a folded protein hydrogel using cryo-scanning electron microscopy (cryo-SEM). BSA was selected because it is a cost-effective, simple globular protein. We show that cryo-SEM can be successfully used to image the structure of the hydrogels at the micrometre and mesoscale. By preparing very thin samples, transmission electron microscopy (TEM) will be used to directly image and explore the protein clusters and their interconnections.

The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.