Abstract
Cell migration is crucial for both physiological and pathological processes. Current in vitro cell motility assays suffer from various drawbacks, including insufficient temporal and/or optical resolution, or the failure to include a controlled chemotactic stimulus. Here, we address these limitations with a migration chamber that utilizes a self-sustaining chemotactic gradient to induce locomotion through confined environments that emulate physiological settings. Dynamic real-time analysis of both population-scale and single-cell movement are achieved at high resolution. Interior surfaces can be functionalized through adsorption of extracellular matrix components, and pharmacological agents can be administered to cells directly, or indirectly through the chemotactic reservoir. Direct comparison of multiple cell types can be achieved in a single enclosed system to compare inherent migratory potentials. Our novel microfluidic design is therefore a powerful tool for the study of cellular chemotaxis, and is suitable for a wide range of biological and biomedical applications.
Highlights
Cell migration plays an important role in diversephysiological processes, including inflammation, wound healing, angiogenesis and cancer metastasis [1,2,3,4]
The microchannels were aligned in a ladderlike configuration orthogonally to and connected to two larger main channels which serve as a cell seeding source and a chemokine reservoir
We demonstrate the use of a PDMS-based microfluidic migration chamber for the real-time observation of chemotaxis of cell populations at single cell resolution
Summary
Cell migration plays an important role in diverse (patho)physiological processes, including inflammation, wound healing, angiogenesis and cancer metastasis [1,2,3,4]. Commonly used in vitro assays, such as the modified Boyden chamber or transwell assay provide end-point data but no information on cell behavior between the start and conclusion of the experiment [7,8]. The wound-healing assay is another popular in vitro method for measuring cell motility on planar twodimensional (2D) surfaces [8]. This assay provides realtime data, it requires a confluent cell monolayer, which precludes the analysis of individual cell movement, and is incompatible with cell types that do not naturally form monolayers. Wound-healing experiments suffer from temporal limitations, are complicated by the effect of cell doubling, and fail to incorporate a chemotactic stimulus for the study of directed cell locomotion
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