Abstract
In vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels—from the proximal to the distal chamber. Myoblast migration was examined in microfluidic devices with varying microchannel widths of 1.5–20 µm, and in chips with uniform microchannel widths over time spans that are relevant for myoblast-to-myofiber differentiation in vitro. We found that the likelihood of spontaneous myoblast migration was microchannel width dependent and that a width of 3 µm was necessary to limit spontaneous migration below 5% of cells in the seeded well after 48 h. These results inform the future design of Polydimethylsiloxane (PDMS) microchannel-based co-culture platforms as well as future in vitro studies of myoblast migration.
Highlights
Cell migration is integral to normal physiological function and plays a role in pathological processes such as immune response [1], wound healing [2], and cancer metastasis [3]
To assess spontaneous myoblast migration across microchannels, PDMS-based microfluidic devices were fabricated which offer distinct chambers connected by an array of orthogonal ladder microchannels (Figure 1a)
To assess whether myoblast migration under confinement is enhanced in response to a chemoattractive gradient, we investigated the number of successful cell crossings into the distal chamber in response to hepatocyte growth factor (HGF) and basic fibroblast growth factor across microchannels of different widths
Summary
Cell migration is integral to normal physiological function and plays a role in pathological processes such as immune response [1], wound healing [2], and cancer metastasis [3]. Only one previous report has leveraged the use of microfluidic chambers to study cellular responses of primary human myoblast cells to chemoattractants [18], taking advantage of the stable establishment of gradients across chambers and their chronic maintenance via hydrostatic pressure. It fails to incorporate dimensional complexity, which aim to recapitulate cell responses in confined spaces. Insight on cellular migration behavior over a range of mechanisms is required to elucidate the complexity associated with the directed process of myogenesis
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