Profiling migration of human monocytes in response to chemotactic and barotactic guidance cues

• Published in: Cell reports methods 2024-09, Vol.4 (9), p.100846, Article 100846
• Main Authors: Hall, Clare K., Barr, Olivia M., Delamare, Antoine, Burkholder, Alex, Tsai, Alice, Tian, Yuyao, Felix E. Ellett, Li, Brent M., Tanzi, Rudolph E., Jorfi, Mehdi
• Format: Article
• Language: English
• Subjects: cell migration; chemotaxis; microfluidic; monocytes; peripheral immune cells
• ISSN: 2667-2375; 2667-2375
• DOI: 10.1016/j.crmeth.2024.100846

Monocytes are critical to innate immunity, participating in chemotaxis during tissue injury, infection, and inflammatory conditions. However, the migration dynamics of human monocytes under different guidance cues are not well characterized. Here, we developed a microfluidic device to profile the migration characteristics of human monocytes under chemotactic and barotactic guidance cues while also assessing the effects of age and cytokine stimulation. Human monocytes preferentially migrated toward the CCL2 gradient through confined microchannels, regardless of donor age and migration pathway. Stimulation with interferon (IFN)-γ, but not granulocyte-macrophage colony-stimulating factor (GM-CSF), disrupted monocyte navigation through complex paths and decreased monocyte CCL2 chemotaxis, velocity, and CCR2 expression. Additionally, monocytes exhibited a bias toward low-hydraulic-resistance pathways in asymmetric environments, which remained consistent across donor ages, cytokine stimulation, and chemoattractants. This microfluidic system provides insights into the unique migratory behaviors of human monocytes and is a valuable tool for studying peripheral immune cell migration in health and disease. [Display omitted] •The MAP chip profiles migration of human monocytes under various chemotactic and barotactic cues•Monocytes preferentially migrate toward CCL2 gradients, regardless of migration pathway and donor age•IFN-γ reduces human monocyte chemotaxis, velocity, and CCR2 expression•Human monocytes show biased migration toward low-hydraulic-resistance pathways Cell migration is fundamental to the biological processes that drive health and disease. While in vivo models provide invaluable insights into cell migration within complex biological environments, precise control over the microenvironment and single-cell tracking is essential to deepen our understanding of the fundamental characteristics of cell migration. We present a high-throughput microfluidic platform, termed the migration analysis of peripheral immune cells (MAP) chip, that features four distinct sets of microchannels designed to assess the effects of both chemotactic and barotactic stimuli on cell migration at a single-cell level. By profiling human monocyte migration using the MAP chip, we demonstrated the utility of this device in characterizing migration of human monocytes under diverse conditions. Hall et al. introduce the MAP chip, a microfluidic platform for profiling human monocytes under