A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells

Abstract

Chemotaxis is the ability to migrate towards the source of chemical gradients. It underlies the ability of neutrophils and other immune cells to hone in on their targets and defend against invading pathogens. Given the importance of neutrophil migration to health and disease, it is crucial to understand the basic mechanisms controlling chemotaxis so that strategies can be developed to modulate cell migration in clinical settings. Because of the complexity of human genetics, Dictyostelium and HL60 cells have long served as models system for studying chemotaxis. Since many of our current insights into chemotaxis have been gained from these two model systems, we decided to compare them side by side in a set of winner-take-all races, the Dicty World Races. These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses. These races bring together technological innovations in genetic engineering and precision measurement of cell motility. Fourteen teams participated in the inaugural Dicty World Race 2014 and contributed cell lines, which they tuned for enhanced speed and chemotactic accuracy. The race enabled large-scale analyses of chemotaxis in complex environments and revealed an intriguing balance of speed and accuracy of the model cell lines. The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis, while the challenges of the first race will guide further technological development and planning of future events.

SiMA: A simplified migration assay for analyzing neutrophil migration

“…Recent attempts to overcome the issue of specialized equipment were successful by producing m-fluidic devices in house; however, still requiring specialized knowledge and equipment to perform soft lithography (22,23,25,26,32). It is, however, still very cumbersome to obtain detailed information on the trajectories of neutrophils, due to the fact, that either only endpoint measurements exist (e.g., under agarose assay) or the required equipment for m-fluidic assays is very specialized (e.g., TAXI-Scan).…”

Cancer cell motility: lessons from migration in confined spaces

“…However, little is known about the inputs of a directional decision-making process in regions that present cells with different paths for cell migration. Chemical-gradient sensing has a role in neutrophil-like cell navigation of microfabricated mazes 98 . In the absence of CDC42 activity, dendritic cells are unable to migrate in vivo , but are still able to polarize and form protrusions in response to chemotactic cues 99 .…”

Rac‐GTPases and Rac‐GEFs in neutrophil adhesion, migration and recruitment

“…1,2 For recruitment, neutrophils adhere to the inflamed blood vessel wall and migrate through it into inflamed tissues. 1 As the fastest migrating vertebrate cell type, 3 they are the rapid-response unit of the immune system. Once arrived at the source of inflammation, they mount pathogen-and debris-clearing effector functions, including degranulation, phagocytosis and the production of both reactive oxygen species (ROS) and neutrophil extracellular traps (NETs).…”

“…In addition, various phosphorylation events modulate its activity [23][24][25] (Figure 5). PIP 3 and Gbc subunits also recruit this GEF to the plasma membrane, [25][26][27] possibly in conjunction with the GPCRadaptor protein Norbin, although this remains to be tested in neutrophils. 28 Like P-Rex1, the Rac-GEF DOCK2 signals in response to GPCR stimulation.…”