Abstract
We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.
Highlights
Chemotaxis is the process by which cells migrate along a concentration gradient towards a chemoattractant
Spheroids are viable inside the microfluidic device We compared the viability of cells within the spheroids inside the microfluidic device to those in a well-plate plate 24 hours after implantation by treating both with Fluorescein diacetate (FDA)/propidium iodide (PI) solutions to detect viable and dead cells
The results showed how the larger dextran took a longer time to diffuse through the hydrogel. Many of these fetal bovine serum (FBS) growth factors have a molecular weight within this 10 kDa–70 kDa range [38], these results provide a good model for the time-scale of the diffusion profile and show the influence of molecule size on gradient evolution
Summary
Chemotaxis is the process by which cells migrate along a concentration gradient towards a chemoattractant. Chemotaxis plays a critical role in many pathologies, including inflammation [1,2,3] and autoimmune diseases [4] as well as cancer [4,5,6,7], and many developmental and tissue remodeling processes, including embryogenesis and wound healing [8, 9]. Techniques that enable detailed scrutiny of the chemotactic process are important tools for drug discovery as well as basic biology. A number of different protocols are used to study cell migration and chemotaxis. The Boyden chamber assay [10] has been one of the most popular assays to study chemotactic response.
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