A comparison of strain and fluid shear stress in stimulating bone cell responses—a computational and experimental study

Abstract

Bone undergoes continuous remodeling in response to mechanical loading. However, the underlying mechanisms by which bone cells respond to their changing mechanical environment, that is, strain in the load-bearing matrix or fluid flow through the canalicular network, are not well understood. It has been established in vitro that bone cells respond differently to substrate strain and fluid shear stress treatments. Uncovering the mechanical basis of these differences represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. To investigate this problem, we developed a biomechanical model of an adherent cell, to test the hypothesis that bone cells respond differently to 0.6 Pa fluid shear stress and 1,000 mu(epsilon) substrate strain stimulation because of qualitative and quantitative differences in the cellular deformation caused. Fluid shear stress loading conditions resulted in maximum displacements at the apical surface of the cell approximately 8 times higher than those due to strain at the cell-substrate interface and also caused higher stressing of all parts of the cell. Significantly, this shows that the deforming effects of fluid shear stress and strain on a cellular level are qualitatively different, which may provide a basis for explaining differences in bone cell responses to both stimuli as reported in several studies. Although our approach to modeling the morphology and complex physical environment of an adherent cell is certainly simplified, our results do show independent roles for fluid flow and strain as mechanical stimuli and highlight the importance of deformation on a cellular level in bone physiology.

Biomechanical analysis of structural deformation in living cells

“…2.3 ( Fig. 5) [55]. In contrast to substrate tension, where the greatest cell strain occurs along the basal surface, fluid shear generates greatest cell distortion on the apical surface.…”

“…Both cone-and-plate and parallel plate flow chambers have been employed in conjunction with cells cultured in monolayer [15,16,69]. Important studies have utilised computational finite element modelling techniques to calculate the cell deformation associated with different magnitudes of fluid shear stress [55]. This biophysical modelling approach utilises existing theoretical models, such as the tensegrity model described by Ingber and others [56,82].…”

“…A cell chamber containing approximately 1 mL of cell suspension permits the entry of the micropipette through a side wall. The micropipette is fixed to the stage of an inverted microscope and connected to a reservoir and a micro-injector via an [55] in-line pressure transducer. Both the micropipette and the pressure control system need to be filled with a physiological saline solution, such as phosphate buffered saline (PBS).…”

Preclinical models for in vitro mechanical loading of bone-derived cells

“…intracellular calcium release 10,32 ), minutes (extracellular ATP release 3 ) or in the first hour (e.g. nitric oxide and PGE 2 release 24,30 ). Flow regimens are rarely performed above 24 h (continuous and intermittent).…”

“…3,24 Also, while bone contains multiple cell types at different stages of differentiation, in vitro models allow for the effects of loading to be studied on individual cell types at specific stages of the differentiation process. 25 A common criticism of in vitro studies is that the substrate and the surroundings of the cell are too different to the bone microenvironment for findings obtained to be relevant.…”