Systems-mechanobiology of health and disease

Experimental biologists study diseases mostly through their abnormal molecular or cellular features. For example, they investigate genetic abnormalities in cancer, hormonal imbalances in diabetes, or an aberrant immune system in vascular diseases. Moreover, many diseases also have a mechanical component which is critical to their deadliness. Most notably, cancer kills typically through metastasis, where the cancer cells acquire the capability to remodel their adhesions and to migrate. Solid tumours are also characterised by physical changes in the extracellular matrix – the material surrounding the cells. While such physical changes are long known, only relatively recent research revealed that cells can sense altered physical properties and transduce them into chemical information. An example is the YAP/TAZ signalling pathway that can activate in response to altered matrix mechanics and that can drive tumour phenotypes such as the rate of cell proliferation.
Systems-biology models aim to study diseases holistically. In this talk, I will argue that physical signatures are a critical part of many diseases and therefore, need to be incorporated into systems-biology. Crucially, physical disease signatures bi-directionally interact with molecular and cellular signatures, presenting a major challenge to developing such models. I will present several examples of recent and ongoing work aimed at uncovering the relations between mechanical and molecular/cellular signatures in health and disease. I will discuss how blood vessel cells interact mechano-chemically with each other to regulate the passage of cells and nutrients between blood and tissue and how cancer cells grow and die in response to mechanical and geometrical stimuli.