Research

Spread and progression of the tumour plays a crucial role, through the dynamic overlap between tumour cells and the extracellular matrix. CARES brings together leading academic and non-academic experts in the fields of matrix biology, biomaterials, microfluidics and cancer research to provide an accurate tool for assessing the response of cancer cells to a variety of anticancer drugs. As a proof-of-concept, we will use breast cancer cells as a model system, with the prospect of extending the system to other cancers. extending the system to other cancers. Our ultimate goal is to develop a novel and user-friendly platform that mimics the human tumour microenvironment in early and advanced stages of cancer by resembling the human tumour microenvironment in early and advanced stages of cancer and can predict with unprecedented accuracy the response of tumour cells to response of tumour cells to cancer therapies in vivo. This will facilitate the development and testing of new drugs and narrow the gap between translational cancer research and targeted cancer therapy, which will have a significant impact on society and the economy. The ambitious scientific goal will provide the backdrop for intensive cross-sectoral and interdisciplinary training of young scientists, providing them with an excellent translational research portfolio that will enable them to succeed in both academia and industry.

In 2025 around 11 billion tonnes of plastic waste will pollute the environment. Therefore, a circular economy with biotransformation and biodegradation of oil-based plastics is as crucial as implementing biobased and biodegradable materials. Transforming lignocellulosic waste biomass into commercially valuable “green” materials is an emerging and promising way to minimize waste, substitute plastic and reduce our carbon footprint. As a waste resource, we suggest walnut shells, in which we discovered the interlocked 3-D puzzle cells. The homogeneity, the high surface area and the channels make these cells interesting for transformation into biodegradable bioplastic. We plan to dissolve the walnut shells in deep eutectic solvent to separate the cells, add water to regenerate lignin and recycle the solvent. The result of this closed process circle is a NUT slurry as a basis for our materials. To tailor and functionalize the composite for different applications we propose to add bacterial cellulose pellicles, a waste from kombucha fermentation or produced in bioreactors. The pure cellulose fibrils with high tensile strength are an exciting counterpart to the high lignin content pressure optimised puzzle cells. With different ratios of the two agri-residues we will tune the material properties for NUTplastic and NUTleather. Sustainable, energy and resource efficient, biodegradable NUTmaterials with a low carbon and environmental footprint are envisaged for the packaging and textile sector. The project activities comprise 1) development and characterisation of NUTleather and NUTplastic products at the demonstration level 2) life cycle analysis, cost of goods and carbon footprint, 3) define endusers, market analysis, potential industrial partner, buisness plan and IP strategy.

Research context / Theoretical framework Controlling and understanding adhesion of cells on artificial surfaces remains as a critical topic in materials and life sciences. In this regard, combination of top-down (contact printing) and bottom-up approaches (ATRP polymerization + layer-by-layer adsorption of polyelectrolytes and proteins) appears as a promising strategy for the design and fabrication of cell-appealing interfaces. Interestingly, this methodology allows going from 2D to 3D-like hierarchical structures of hybrid content (niches) that influence a subsequent cell attachment on top, by better exposing the specific binding sites (RGD, IKVAV moieties) towards target membrane receptors (i.e. integrins, CD44). Complementary use of Atomic Force Microscopy (AFM), with a living cell as probe, together with Quartz Crystal Microbalance with Dissipation (QCM-D), will enable an early-stage analysis and quantification of these cell-substrate interactions on the nanoscale. Hypotheses/ Research questions / Objectives The main hypotheses of the project are the following: i) Combination of substrate-anchored polymer brushes and layer-by-layer deposited polyelectrolyte chains give rise to soft 3D niches for the enhanced adsorption of ECM proteins. The transformation of 2D interfaces into 3D-like architectures will, in turn, enhance cell attachment and proliferation of cells, with particular impact on both cell morphology and the number of cell-substrate connections formed; ii) The use of Contact-Printing techniques before the grafting-from of the brushes allows the fabrication of localized individual 3D attachment points. The localized presence of specific molecules will influence the cell-substrate affinity with final impact on cell morphology and the establishment of a different number of cell-surface contacts; iii) Single-Cell Probe Force Spectroscopy (SCPFS) technique is sensitive enough to identify early stage attachment events in cell-substrate contacts. The use of a living cell acting as indenting probe will determine events taking place on the nano- and microscale. Approach / Methods The following methods will be used to study substrate preparation and cell adhesive behaviour: Atomic force microscopy (AFM) in SCPFS mode, (confocal) fluorescence microscopy, quartz crystal microbalance with dissipation (QCMD), scanning electron microscopy (SEM), and cell culture protocols.