On-Chip Quantitative Measurement of Mechanical Stresses During Cell Migration with Emulsion Droplets

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.

Oncoimmunology Meets Organs-on-Chip

“…A first example of such studies was provided by Molino and co-Workers. They described a CC system properly designed to follow leukemic cell migration toward an oil droplet ( Molino et al, 2016 ). For some aspects, these droplets resemble immune cell moving in the CC microchannel.…”

Microfabricated tissues for investigating traction forces involved in cell migration and tissue morphogenesis

“…The role of traction forces in the migration of individual cells has been studied in fibroblasts [8], epithelial cells [45], Dictyostelium cells [50], cancer cells [9,73], myoblasts [74], neutrophils [75], dendritic cells [76], keratinocytes [77], and bovine aortic endothelial cells [47], among others. Cells on 2D planar surfaces were found to exert both in-plane and normal tractions as they migrated (Figure 1A).…”

Microfluidic platform for probing cancer cells migration property under periodic mechanical confinement

“…the testing results. Specifically, in day 9, the average migration distance of OCI-AML cells was 911.6 6 114.7 lm (mean 6 S.D., N ¼ 30) in the 10-constriction chip, which was greater than 816 5. 6 103.9 lm (mean 6 S.D., N ¼ 30) in the 5-constriction chip and 229.3 6 95.1 lm (mean 6 S.D., N ¼ 20) in the microchannels without constriction.…”

“…3 Recent developments in microfluidic technology have allowed the observation of individual cell migration with high spatial and temporal resolution. [4][5][6][7][8] Several microfluidic devices have been developed to mimic the microenvironment of cell migration. 3,5 To investigate the migration of cancer cells, many microfluidics-based studies focused on the role of soluble chemoattractant gradients 9,10 and electrical field in directed cancer cell migration.…”

“…[4][5][6][7][8] Several microfluidic devices have been developed to mimic the microenvironment of cell migration. 3,5 To investigate the migration of cancer cells, many microfluidics-based studies focused on the role of soluble chemoattractant gradients 9,10 and electrical field in directed cancer cell migration. [11][12][13][14] On the other hand, since cancer cells physically interact with their surrounding environment during metastasis at different stages, 15 an investigation of physical cues, in the form of adhesion gradients 16 or patterned surfaces, 17 is also important to study cell migration property.…”