Time-dependent deformations in bone cells exposed to fluid flow in vitro: investigating the role of cellular deformation in fluid flow-induced signaling.

Numerous experiments have shown fluid flow to be a potent stimulator of bone cells in vitro, suggesting that fluid flow is an important physical signal in bone mechanotransduction. In fluid flow experiments, bone cells are exposed to both time-dependent (e.g., oscillating or pulsing) and time-independent (e.g., steady) flow profiles. Interestingly, the signaling response of bone cells shows dependence on loading frequency and/or rate that has been postulated to be due to viscoelastic behavior. Thus, the objective of this study was to investigate the time-dependent deformations of bone cells exposed to fluid flow in vitro. Specifically, our goal was to characterize the mechanical response of bone cells exposed to oscillatory flow from 0.5 to 2.0 Hz and steady flow, since these flow profiles have previously been shown to induce different morphological and biochemical responses in vitro. By tracking cell-bound sulfate and collagen coated fluorescent beads of varying sizes, we quantified the normalized peak deformation (peak displacement normalized by the maximum peak displacement observed for all frequencies) and phase lag in bone cells exposed to 1.0 Pa oscillating flow at frequencies of 0.5-2.0 Hz. The phase lag was small (3-10 degrees ) and frequency dependent, while the normalized peak displacements decreased as a weak power law of frequency ( approximately f(-0.2)). During steady flow, the cells exhibited a nearly instantaneous deformation, followed by creep. Our results suggest that while substantial viscous deformation may occur during steady flow (compared to oscillating flow at approximately 1 Hz), bone cells behave primarily as elastic bodies when exposed to flow at frequencies associated with habitual loading.