The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

Anderson, Eric J.; Falls, Thomas; Sorkin, Adam M; Tate, Melissa L. Knothe

doi:10.1186/1475-925x-5-27

Cited by 46 publications

(39 citation statements)

References 47 publications

(46 reference statements)

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“…In previous computational studies of PPFC systems, it is the shear stress that is considered to dominate the applied mechanical stimulus. A number of CFD simulations have highlighted amplifications in the target WSS along the cell membrane [21][22][23], similar to that observed in our local FSI model (figure 4a), however do not consider the potentially significant contribution of pressure acting on the cell membrane. If cellular response under fluid flow is assumed to be a strain-activated mechanism, then the local FSI model results herewith are in agreement with the experimental studies of Huesa et al [16] who predicted that the stimulation of cells in a PPFC was probably a result of a combined stimulus of pressure and WSS.…”

Section: Discussionsupporting

confidence: 74%

“…To date, the main design criteria associated with PPFCs has been to establish a suitable homogeneous wall shear stress (WSS) profile in the region where cultured cells are located [20]. Computational fluid dynamics (CFD) approaches have been applied to predict the mechanical stresses acting on a single-cell monolayer [21] and multi-cell monolayer arrays [22,23] under laminar flow in PPFC systems. Such studies have predicted that there is significant amplification of shear stress (approx.…”

Section: Introductionmentioning

confidence: 99%

“…Such studies have predicted that there is significant amplification of shear stress (approx. threefold) imparted on the cell membrane owing to the disturbance of the flow in the vicinity of the cell [21][22][23] and that a large spatial variation of the target WSSs may exist when different flow setups are compared [22]. As such, comparing outcomes of specific cell responses may not be appropriate between different PPFC systems.…”

Section: Introductionmentioning

confidence: 99%

“…As such, comparing outcomes of specific cell responses may not be appropriate between different PPFC systems. Furthermore, the appropriateness for such systems in replicating the in vivo loading environment remains unclear, since the applied in vitro mechanical stimulus are not well defined [22]. Experimental observation of osteocytes subject to in vitro fluid flow have shown that different cells within a monolayer may not be receiving the same mechanical stimulus resulting in different levels of intracellular calcium and NO expression within the cell population [12].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

Vaughan

Haugh

McNamara

2013

J. R. Soc. Interface.

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Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment and strain-induced flow of interstitial fluid is believed to be the primary mediator of mechanical stimuli to bone cells in vivo. In vitro investigations have shown that bone cells produce important biochemical signals in response to fluid flow applied using parallel-plate flow chamber (PPFC) systems. However, the exact mechanical stimulus experienced by the cells within these systems remains unclear. To fully understand this behaviour represents a most challenging multi-physics problem involving the interaction between deformable cellular structures and adjacent fluid flows. In this study, we use a fluid-structure interaction computational approach to investigate the nature of the mechanical stimulus being applied to a single osteoblast cell under fluid flow within a PPFC system. The analysis decouples the contribution of pressure and shear stress on cellular deformation and for the first time highlights that cell strain under flow is dominated by the pressure in the PPFC system rather than the applied shear stress. Furthermore, it was found that strains imparted on the cell membrane were relatively low whereas significant strain amplification occurred at the cell -substrate interface. These results suggest that strain transfer through focal attachments at the base of the cell are the primary mediators of mechanical signals to the cell under flow in a PPFC system. Such information is vital in order to correctly interpret biological responses of bone cells under in vitro stimulation and elucidate the mechanisms associated with mechanotransduction in vivo.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

Vaughan

Haugh

McNamara

2013

J. R. Soc. Interface.

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“…More importantly, due to the high resolution of our local sub-scaffold FSI model, it was shown that the WSS was amplified significantly at the cell level when compared to the predicted WSS from the global model, with certain cases exhibiting a five-fold increase. Interestingly, similar cell level amplification effects of WSS have been observed for 2D cell perfusion systems (Anderson et al 2006;Vaughan et al 2013). However, in 2D cell perfusion systems, the WSS magnitudes to stimulate a biochemical response of cells in osteogenic and chondrogenic differentiation were much higher than the levels of WSS in our study.…”

Section: Discussionsupporting

confidence: 69%

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

Zhao

Vaughan

McNamara

2014

Biomech Model Mechanobiol

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For attached and bridged osteoblasts, the maximum strains are 397µε and 177,200µε, respectively.Additionally, the results from mechanical compression show that attached cells are more stimulated (maximum strain=22,600µε) than bridged cells (maximum strain=10,000µε). Such information is important for understanding the biological response of osteoblasts under in vitro stimulation. Finally, a combination of perfusion and compression of a TE scaffold is suggest for osteogenic differentiation.

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Modeling of shear stress experienced by endothelial cells cultured on microstructured polymer substrates in a parallel plate flow chamber

Brown

Burke

Meenan

2011

Biotech & Bioengineering

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The application of physical stimuli to cell populations in tissue engineering and regenerative medicine may facilitate significant scientific and clinical advances. However, for the most part, these stimuli are evaluated in isolation, rather than in combination. This study was designed to combine two physical stimuli. The first being a microstructured tissue culture polystyrene substrate, known to produce changes in cell shape and orientation, and the second being laminar shear stress in a parallel plate flow chamber. The combined effects of these stimuli on endothelial cell monolayers cells were evaluated in a parallel plate flow chamber and using a computational fluid dynamics (CFD) model. The topography of the cell monolayers cultured on different microstructured surfaces was determined using confocal laser scanning microscopy (CLSM), and this topographic information was used to construct the CFD model. This research found that while the specific underlying structures were effectively planarized by the cell monolayer, significant differences in cell shape and orientation were observed on the different microstructured surfaces. Cells cultured on grooved substrates aligned in the direction of the grooves and showed higher retention after 1-h LSS conditioning than those cultured on pillars. The modeled shear stress distributions also showed differences. While minor differences in the magnitude of shear stress were noted, aligned cell monolayers experienced significantly lower spatial gradients of shear stress when compared with cells that were not pre-aligned by surface features. The results presented here provide an analysis of how one form of physical stimulus can be moderated by another and also provide a methodology by which the understanding of cell responses to topographic and mechanical stimuli can be further advanced.

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The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

Cited by 46 publications

References 47 publications

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

A fluid–structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

Modeling of shear stress experienced by endothelial cells cultured on microstructured polymer substrates in a parallel plate flow chamber

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