The last decade has brought extensive evidence demonstrating that mechanical forces transmitted through cell-matrix and cell-cell adhesions drive fundamental processes in development, tumourigenesis, and wound healing. A major potential in oncology, regenerative medicine, and biomaterial design could thus be harnessed by the understanding and control of biological adhesion and mechanics. However, such understanding and control remain unattained as they require the generation of knowledge and technologies operating hierarchically from the scale of molecules to that of organs. This technology is currently unavailable due to the complexity, multi-scale nature, and interdisciplinarity of the phenomena involved. At the nanometre level, cells adhere to other cells and their surrounding extracellular matrix through specific molecules such as integrins or cadherins. The nano-mechanical properties under force of adhesive molecular links determine cell response and the activations of oncogenes such as YAP. At the micrometre level, the collective action of adhesive molecules enables cells not only to remain cohesive with their environment but to actively feel and respond to it, by combining both biochemical signalling and biophysical responses to mechanical forces. At the millimetre level, the again collective action and interactions among large ensembles of cells generates emerging behaviours that define tissue architecture and function. At the meter scale the adhesive interactions acting at the molecular, cellular, and tissue level integrate to enable functional organs, and functional organisms. Our expected results are the construction of a body of knowledge and technology that encompasses biomechanics from the single molecule to whole organ scale, and the demonstration that it can be harnessed to control biological function in general, and breast cancer in particular. This will include scientific knowledge, experimental and computational technologies spanning from the molecule to the organism. Consequently, we aim to provide a rigorous, mechanistic and technologic baseline for tissue mechanics and cohesiveness with the potential to control and predict the outcome of any morphogenetic process. We will focus on breast cancer as a proof-of-concept system. Since mechanical forces transmitted through adhesive links are crucial in cancer, development, and wound healing, approaches based on inhibiting adhesion (for oncology applications) and on promoting it (for implants) have already been attempted. However, those approaches often fail because merely inhibiting adhesion in a tumour may promote metastasis, and because certain types of adhesion in implants may promote rejection. Because we have no mechanistic knowledge of how mechanics and adhesion drive biological response, current development is based on trial-and-error approaches, often leading resource waste and ineffective results. We propose to shift this paradigm, providing the techniques and mechanisms that will allow not merely to inhibit or promote adhesion, but to steer and tune mechanical and adhesive signals in the proper direction. Our developed hydrogels, with the potential ability to tune adhesive and mechanical properties, have a major potential to be used in drug screening in cancer. This potential is further enhanced by all the biological characterization work being carried out by the consortium. We have identified a particularly promising molecular interaction involved in mechanical responses, and we are developing drugs to target it.
