Abstract
During metastasis, cancerous cells leave the primary tumour, pass into the circulatory system, and invade into new tissues. To migrate through the wide variety of environments they encounter, the cells must be able to remodel their cell shape efficiently to squeeze through small gaps in the extracellular matrix or extravasate into the blood stream or lymphatic system. Several studies have shown that the nucleus is the main limiting factor to migration through small gaps (Wolf et al., 2013; Harada et al., 2014; Mak et al., 2013). To understand the physical limits of cancer cell translocation in confined environments, we have fabricated a microfluidic device to study their ability to adapt their nuclear and cellular shape when passing through small gaps. The device is open access for ease of use and enables examination of the effect of different levels of spatial confinement on cell behaviour and morphology simultaneously. The results show that increasing cell confinement decreases the ability of cells to translocate into small gaps and that cells cannot penetrate into the microchannels below a threshold cross-section.
Highlights
Cell migration mediates a number of physiological and pathological processes and is an essential feature of cancer metastasis
Cells are confronted to different levels of physical confinement, moving across pores with a cross section ranging from 10 to
To study the effects of physical confinement in a non-pliable and non-degradable environment, we have developed microfluidic devices with arrays of micro-channels of different cross-sectional areas
Summary
Cell migration mediates a number of physiological and pathological processes and is an essential feature of cancer metastasis. Cancer cells leave the primary tumour, extravasate into the blood stream, intravasate into new tissues, and migrate to form new colonies (Fig. 1) Throughout this process, they encounter many different extracellular environments and must show great plasticity in their migratory strategies. Cancer cells are known to adapt their migratory strategies in response to extracellular cues in order to cross basement membranes and connective tissues [4] During these processes, cells are confronted to different levels of physical confinement, moving across pores with a cross section ranging from 10 to. MDA MB 231 human breast cancer cells were induced to migrate through the channels while the cellular and nuclear morphology was imaged This allowed us to characterise the cells’ ability to adapt to different degrees of confinement and to study the deformation of the cytoplasm and the nucleus in conditions where proteolysis of the extracellular matrix can be disregarded. Cellular and nuclear deformations are studied while cells translocate from the reservoir into the micro-channels
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