Heterogeneity in the mechanical properties of integrins determines mechanotransduction dynamics in bone osteoblasts

Aban Shuaib, Daniyal Motan, Pinaki Bhattacharya, Alex Mcnabb, Timothy M. Skerry & Damien Lacroix

We know that the effect on the skeleton of brief periods of exercise persists for over 24 hours – effectively bone remembers what loads it has experienced and uses that information to adapt its structure.  This tunes the skeleton to become strong enough to support habitual loads and provide a safety factor so that it should not break in normal use.  The mechanism behind bone load memory is difficult to explore because many very complex experiments would be needed to test each idea.  Here we have developed a computer model to explore the way that different signals could provide long-lasting influences on bone cells to fit with the timing of their ability to respond and influence bone structure.  Cells in bone are attached to the hard mineralised material by molecules called integrins and we have modelled the effect of different sensitivity of those integrins to deformation of bone due to loading.  Our model follows the change from a mechanical event in bone to biochemical signals within the cell that can control other cells which make or remove bone.  This research is important because age reduces the sensitivity of bone to exercise stimuli, so understanding this mechanism may lead towards ways to maintain or increase bone strength in older people, where fracture is a growing problem.

A hybrid multi-scale model of mechanotransduction combining an agent based model (ABM) and a mechanical model

Shuaib, A., Motan, D., Bhattacharya, P., McNabb, A., Skerry, T. M., Lacroix, D. (2019), “Heterogeneity in The Mechanical Properties of Integrins Determines Mechanotransduction Dynamics in Bone Osteoblasts”, Scientific Reports, 9, Article number: 13113

URL: https://doi.org/10.1038/s41598-019-47958-z