Figure 5
Mechanosensitivity heterogeneity in integrin population, contributes to the emergence of molecular mechanical memory of previous mechanical stimulation. The overall activation dynamics exhibited by the 1% HM Mech-ABM, during constant unidirectional shear stress mechanical stimulation. (A) A representation of active integrin levels over 24 h. Integrin activation was triphasic characterised by an accelerated activation at the initial phase (0–60 min), followed by deactivation phase and succeeded by a sustained activation phase which was maintained beyond 24 h. (B) Activated ERK (pERK) also demonstrated a triphasic activation behaviour, where the initial phase was characterised by ultrasensitive response to reach Emax within 6.69 ± 3 min. The maximal pERK levels were briefly maintained (100 ± 11 min) followed by gradual reduction. The third phase was characterised by the maintenance of pERK levels and the establishment of a new pERK baseline that lasted >96 h (4 days). This baseline was 80 ± 20 fold increase of pERK levels at t0 and 3 ± 0.8% of its Emax. Although the 1% ultrasensitive integrin population was unable to maintain high level of pERK, however, it was capable of maintaining an adequate level of pERK beyond 24 h (and 4 days). (C) Graph representing the formation of and deposition of three ECMps over time from 16 simulations and represented as median ± IQR. (D) Stacked bars illustrating the accumulation of the four ECMps (OPN, OCN, ALP and BSP) at hourly intervals over 24 h. The points shown are from 16 simulations (n = 16) representing median ± IQR.
