Abstract
We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF) chemoattraction in a gradually tapered space, imposing mechanical stresses. The device consisted of two 5-mm-diameter chambers connected by ten 600 µm-long and 10 µm-high tapered microchannels. The taper region gradually changes the width of the channel. The channels tapered from 20 µm to 5 µm over a transition length of 50 µm at a distance of 250 µm from one of the chambers. The chemoattractant drove cell migration into the narrow confines of the tapered channels, while the mechanical gradient clearly altered the migration of cells. Cells traversing the channels from the wider to narrow-end and vice versa were observed using time-lapsed imaging. Our results indicated that the impact of physical stress on cell migration patterns may be cell type specific.
Highlights
Cancer cells at the primary tumor site(s) acquire the ability to migrate to a distant site to form a secondary tumor characterize cancer metastasis
It has been reported that the metastasis of breast cancer, is mediated by the stimulation of chemokines and transforming growth factor beta (TGFβ) [2,3,4,5,6,7,8,9,10]
We have previously reported the design of a microfluidic device by which we provided evidence of: (1) the establishment and maintenance of a chemical gradient in the device; and
Summary
Cancer cells at the primary tumor site(s) acquire the ability to migrate to a distant site to form a secondary tumor characterize cancer metastasis. It is conceivable that the alteration of gene expression occurs in the metastatic cells to accommodate specific enzymatic digestion of embedding extra-cellular matrix (ECM), to gain the ability for extra- and intra-vasation, through the blood and lymphatic vessel walls These cellular responses may have resulted from biochemical stimulation and/or mechanical force-induced signal transduction. Individual cells rely on the intrinsic redistribution of cellular molecules/components to migrate in response to gradients of extrinsic signals [50,51] These signals include chemical, spatial physical stresses or electromagnetic stimulations [50,51,52,53,54]. The narrower channels amplify the physical stresses and impact the cell structure, causing significant changes in the migration behavior of the cells This is clearly demonstrated by comparing with migration patterns observed in a uniform channel study, previously reported in [48,49]. The cells migrated across the entire length of the channel, entered the open chamber on the other end and continued to proliferate
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