Figure 3
Alteration of the integrin mechanosensitivity threshold impacts mechanotransduction dynamics and maintenance. Representation of the mechanotransduction behaviour of Sensitive (SM) and Ultrasensitive (USM) Mech-ABMs within the initial 60 min and beyond 8 h of mechanical stimulation. (A) Integrin activation dynamics were not statistically different in SM and USM during the initial 60 min of activation. Integrin population in the SM were activated by the mechanical stimulus in the initial phase (0–60 min), this activation behaviour was followed by gradual reduction leading to complete inactivity within the initial 180 ± 20 min. Conversely, in USM, integrins detection and activation by mechanical stimulation was maintained beyond 96 h (4 days). (B) Mechanotransduction events were examined via monitoring phosphorylated ERK (pERK). In SM, mechanotransduction was maintained until 107 min. Contrariwise, in USM, pERK generation was maintained past 96 h (4 days), although levels were approximately 50% less compared to the initial phase of activation (0–60 min). (C) Stacked bars demonstrating accumulation of the four ECMps (OPN, OCN, ALP and OCN) over 4 Days of mechanical stimulation. The initial activation phase showed no statistical difference between the two models. However, after 150 min levels of ECMp plateau in SM, while ECMp levels continue to increase in the USM. Mechanical stimulation at the tissue level was a constant unidirectional shear stress. OPN, OCN, ALP and BSP abbreviate osteopontin, osteocalcin, alkaline phosphatase and bone sialoprotein respectively. Data shown from one simulation (n = 1). Sensitive model refers to Mech-ABM where integrin mechanosensitivity threshold was 10% of applied force at the tissue level (AFT), while the Ultrasensitive was 1% of AFT.
