Abstract
The ability of immune cells to migrate within narrow and crowded spaces is a critical feature involved in various physiological processes from immune response to metastasis. Several in-vitro techniques have been developed so far to study the behaviour of migrating cells, the most recent being based on the fabrication of microchannels within which cells move. To address the question of the mechanical stress a cell is able to produce during the encounter of an obstacle while migrating, we developed a hybrid microchip made of parallel PDMS channels in which oil droplets are sparsely distributed and serve as deformable obstacles. We thus show that cells strongly deform droplets while passing them. Then, we show that the microdevice can be used to study the influence of drugs on migration at the population level. Finally, we describe a quantitative analysis method of the droplet deformation that allows measuring in real-time the mechanical stress exerted by a single cell. The method presented herein thus constitutes a powerful analytical tool for cell migration studies under confinement.
Highlights
The ability of immune cells to migrate within narrow spaces is a critical feature involved in various physiological processes from immune response to metastasis
We developed a hybrid microchip made of parallel PDMS channels in which oil droplets, with sizes comparable to cells, are sparsely distributed and serve as deformable obstacles that migrating cells have to squeeze to explore their environment
After a description of the fabrication of the microdevice, we show that neutrophil-like HL-60 cells can cross and squeeze the obstacles while deforming their nucleus
Summary
The ability of immune cells to migrate within narrow spaces is a critical feature involved in various physiological processes from immune response to metastasis. Cells such as neutrophils are required to migrate within constrictions that are much smaller than their own diameter, such as small capillaries The mechanical rigidity of the fabrication materials such as PDMS32 limits the collection of quantitative data related to the physical stress that a cell is able to produce when crossing a constriction during a migration event, pushing for the development of microdevices having softer actuation elements with mechanical properties comparable to those of cells[33]. Since the shape of a droplet is set by the interplay between the interfacial tension and the mechanical stress field acting on it[37,38], a simple microscopic analysis of the deformation of the droplet shape over time brings quantitative information on the mechanical stress that cells are exerting on it
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