Abstract
ABSTRACTCell migration is highly sensitive to fluid shear stress (FSS) in blood flow or interstitial fluid flow. However, whether the FSS gradient can regulate the migration of cells remains unclear. In this work, we constructed a parallel-plate flow chamber with different FSS gradients and verified the gradient flow field by particle image velocimetry measurements and finite element analyses. We then investigated the effect of FSS magnitudes and gradients on the migration of osteoclast precursor RAW264.7 cells. Results showed that the cells sensed the FSS gradient and migrated toward the low-FSS region. This FSS gradient-induced migration tended to occur in low-FSS magnitudes and high gradients, e.g., the migration angle relative to flow direction was approximately 90° for 0.1 Pa FSS and 0.2 Pa mm−1 FSS gradient. When chemically inhibiting the calcium signaling pathways of the mechanosensitive cation channel, endoplasmic reticulum, phospholipase C, and extracellular calcium, the cell migration toward the low-FSS region was significantly reduced. This study may provide insights into the mechanism of the recruitment of osteoclast precursors at the site of bone resorption and of mechanical stimulation-induced bone remodeling.
Highlights
In vivo migration of cells generally occurs under fluid flow in blood vessels or interstitial cavities through metastasis of cancer cells,[1] immune response [2], embryonic development [3], and tissue regeneration [4]
Finite element analysis (FEA) results basing on this model obviously showed fluid shear stress (FSS) gradient along the direction perpendicular to the flow direction, and changing the pressure difference produced the three FSS gradients, namely, 0.05, 0.1, and 0.2 Pa mm−1, respectively (Figure 1(e))
Statistical analysis further verified that the wall FSS based on Particle image velocimetry (PIV) measurements or FEA simulations has linear relationship with the distance along the FSS gradient (Figure 2 (c))
Summary
In vivo migration of cells generally occurs under fluid flow in blood vessels or interstitial cavities through metastasis of cancer cells,[1] immune response [2], embryonic development [3], and tissue regeneration [4]. A large number of in vitro studies basing on microfluidic technology or parallel-plate flow chamber were performed to investigate the effect of fluid shear stress (FSS) on cell migration. Flow stimulation with different chemical concentration gradients showed obvious effect on the migration of nerve cells, endothelial cells, or cancer cells by using microfluidic devices [5,6]. Another study showed that when FSS was exerted on endothelial cells cultured on nanofiber membranes, the cells tended to migrate along the well-aligned nanofiber direction to maintain the integrity of intercellular connections [7]. MDA-MB-231 cancer cells are in high density or inhibit the CCR-7 receptor migrate against the flow direction [8]. The present study reported another unexpected migration of osteoclast precursors under gradient FSS
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