Analysis of mechanotransduction dynamics during combined mechanical stimulation and modulation of the extracellular-regulated kinase cascade uncovers hidden information within the signalling noise

Hybrid Mechanical and Agent Based Model Framework

Osteoporosis is a bone disease that leads to bone fragility and an increased risk of their fracture. By 2025, osteoporosis will cost the NHS over £2.2 billion per year, with limited treatments available to tackle it. Our work aims to help uncover new treatments by finding conditions that improve bones’ health. Healthy bones are maintained by a well-balanced process of building and demolishing at the microscopic scale, and when this is disturbed, osteoporosis develops. So understanding the factors affecting this process and their interactions, will help us realise how osteoporosis develop, and so how to treat it better. Such factors are combined mechanical stimulation and cellular biochemical activity. Our paper use a pioneering computational model and a novel analytical technique to examine combined mechanical and biochemical stimulation. It demonstrated that mRNA production of bone formation markers, though chaotic at first glance, contain within it information about how cells interpret combined mechanical and biochemical stimuli and translate it into production of bone formation markers. The paper proposes a new intracellular targets and regimes to treat osteoporosis.

Ascolani, G., Skerry, T. M., Lacroix, D., Dal’Ara, E., Shuaib, A. (2020), “Analysis of mechanotransduction dynamics during combined mechanical stimulation and modulation of the extracellular-regulated kinase cascade uncovers hidden information within the signalling noise”, Interface Focus, 11(1): 20190136, URL: https://doi.org/10.1098/rsfs.2019.0136