Figure 1
A hybrid multi-scale model of mechanotransduction combining an agent based model (ABM) and a mechanical model. (a) The ABM simulated molecular events downstream of integrin mechanoreceptors in a spherical osteoblast responding to mechanical stimulation imposed at the ECM. The enlarged box shows the cascade simulated by the ABM which focused on biochemical mechanotransduction. This recruited the ERK pathway and its induced osteogenic gene expression events. These involved TF Runx2 recruitment, and its ensemble to express osteogenic ECM genes. Their corresponding mRNA and proteins were produced and the latter were deposited in the surrounding ECM. (b) A representation of the mechanical model; at the tissue level a unidirectional and constant shear stress was applied and was propagated through the ECM. The mechanical force was transferred to the interface between the cell and the ECM, resulting in cell and plasma membrane compression. Integrins resided at the interface, and the opposing stretch forces at the ECM and the plasma membrane were triggers for integrin activation. The values of the forces were computed and quantified by the mechanical model. The enlarged box illustrates the required parameters to calculate the forces generated on individual integrin-agents. The two models communicated every iteration which was equivalent to 1 s. The arrows between the two models represent these communications and the input/output parameters. ECM, ECMp FAK, Ras, Raf, MEK, MAPK, Runx2, Osx, TF, ALP, OCN, OPN, BSP, Ur, r, θ and ϕ stand for: extracellular matrix, extracellular matrix protein, focal adhesion kinase, Rat sarcoma, Rapidly Accelerated Fibrosarcoma protein, Mitogen-activated protein kinase kinase, Mitogen-activated protein kinase, Runt-related transcription factor 2, Ostrix, transcription factor, alkaline phosphatase, osteocalcin, osteopontin, bone sialoprotein, deformation of cell and ECM surfaces, and spherical polar coordinates locations respectively.
