Mechanics, Geometry and Topology of Health and Disease

Date: Monday 4th September 2023

Abstract

Experimental biologists traditionally study healthy biological functions and the progression of diseases predominantly 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. However, many diseases also have a mechanical component which is critical to their deadliness. Notably, cancer kills typically through metastasis, where the cancer cells acquire the capability to remodel their adhesions, generate forces and migrate to distant organs. Solid tumours are also characterised by physical changes in the extracellular matrix – the material surrounding the cells. While such physical changes are long known, and e.g. enable doctors to feel a tumour by palpation, 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, or metastatic behaviour. Another example is blood vessel cells that sense blood flow, material properties of the surrounding environment and forces from neighbouring cells.

In this talk, I will argue that physical signatures are a critical part of many biological systems and therefore, need to be incorporated into mathematical models. 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 the heart’s molecular state changes during ageing, which, consequently, affects heart muscle function. Next, 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 we model these interactions through a contact mechanics model.  Finally, I will discuss how cellular and subcellular geometry, such as cell shape, affects intracellular reaction networks – the networks that control cell behaviour.