Breast cancer development is marked by massive increase of matrix fibres around tumor cells, which changes the mechanical properties of the tissue and is used to diagnose tumours by manual palpation. It is therefore possible that defective mechanical properties of the fibres in the cell microenvironment promote the initiation and progression of tumours.
We aim to determine the molecular mechanisms that control cellular mechanorespons to fibres, cell invasion and cancer growth, for future drug development against cancer. For this, we will use an interdiciplinary strategy combining tumour cell and molecular biology, nanomaterial sciences, fibre and polymer technology, Biomechanics and biomedicine. We will engineer a fibrillar microenvironment, that allows a separate tuning of the material´s chemical and mechanical properties. We will then separately alter these parameters in the presence of normal and oncogenically transformed cells, analyze the cell size, growth, movement, mechanorespons, fibre recruitment, fibre alignment, and identify the underlying cytoskeletal molecular mechanisms of control.
The importance of mechanosensation for the behaviour of cells has been greatly overlooked in the past. Hence, the identification of the molecular mechanisms that control this cell property will significantly increase our understanding of all basic cell functions that depend upon mechanics, e.g. cell deformation, motility, cytokinesis and, thus, of all physiological processes that depend upon these functions, e.g. embryogenesis, tissue homeostasis and cancer. Identification of the molecular mechanisms that control cell invasion via cell mechanics can provide target molecules for future development of anti-metastasis drugs. As these drugs would be based only on mechanics, they can form a previously unknown, mechano-based, class of drugs. As tumor cell invasion and metastasis is the number one cause of cancer deaths, this can improve prevention of human death in cancer.