An electro-osmotic microfluidic system to characterize cancer cell migration under confinement

Abstract

<jats:p>We have developed a novel electro-osmotic microfluidic system to apply precisely controlled osmolarity gradients to cancer cells in micro-channels. We observed that albeit adhesion is not required for cells to migrate in such a confined microenvironment, the migrating velocity of cells is strongly influenced by the interactions between the cells and the channel wall, with a stronger adhesion leading to diminished cell motility. Furthermore, through examining more than 20 different types of cancer cells, we found a linear positive correlation between the protein concentration of the aquaporin-4 (AQP4) and the cell migrating speed. Knockdown of AQP4 in invasive re-populated cancer stem cells reduced their migration capability down to the level that is comparable to their parental cancer cells. Interestingly, these observations can all be quantitatively explained by the osmotic engine model where the cell movement is assumed to be driven by cross-membrane ion/water transport, while adhesion acts as a frictional resistance against the cell motility. By providing versatile and controllable features in regulating and characterizing the migration capability of cells, our system may serve as a useful tool in quantifying how cell motility is influenced by different physical and biochemical factors, as well as elucidating the mechanisms behind, in the future.</jats:p>

Application of microneedles combined with dendritic cell-targeted nanovaccine delivery system in percutaneous immunotherapy for triple-negative breast cancer

“…In addition, it has been found that microacupuncture into the skin can significantly induce epidermal DCs aggregation and migration to the draining lymph nodes [37]. Recent studies have also found that this may be related to the migration of DCs driven by changes in skin osmotic pressure under the action of transdermal mechanical forces [38,39]. The combination of DMNP with DC-targeted nanotechnology is expected to trigger stronger and longerlasting immune responses.…”

Role of Aquaporins in the Physiological Functions of Mesenchymal Stem Cells

“…Other studies have identified AQP4 as the most abundant AQP in nasopharyngeal and lung CSCs and have shown its involvement in the regulation of large volumetric changes related to an increase in death rate [ 155 ]. Using a novel electro-osmotic microfluidic system that controls cell osmolarity gradients, AQP4 expression has been shown to be directly correlated with the speed of cell migration [ 137 ] ( Table 3 ). In addition, when the expression of AQP4 is suppressed via siRNA, the CSC migration capability as well as the expression of stemness biomarkers such as Sox-2 or Oct-4 are significantly reduced.…”

On the coupling of mechanics with bioelectricity and its role in morphogenesis

“…Note that osmosis has already been related to cancer progression in the literature. Specifically, Stroka et al [44] demonstrate that differential osmosis through the leading and trailing edges of a single tumour cell in a narrow channel promotes cell migration; Hui et al [45] show that migration of individual cancer cells in a confined environment, driven by osmotic concentration gradients, is reduced by abating the concentration of aquaporins, suggesting that cancer progression might be hampered by reducing transmembrane osmosis.…”