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A confining microfluidic platform for disparate density coculture reveals the dynamics of macrophage-mediated adipocyte clearance
Summary
Scientists built a tiny lab-on-a-chip device that finally lets them watch immune cells (macrophages) interact with fat cells in real time — something that was previously impossible because fat cells float while immune cells sink and stick to surfaces. They discovered that immune cells team up in clusters to surround and clear away dead, lipid-filled fat cells more effectively than when they act alone, offering new insight into the chronic inflammation seen in obesity. This same technology could also help researchers study how immune cells interact with floating microplastic particles in the body, an emerging health concern.
Abstract Co-culturing cells with mismatched densities, where one cell type adheres to surfaces while the other floats, represents a fundamental challenge in cell biology. This is particularly evident in studying macrophage-adipocyte interactions, where macrophages must engage and clear lipid-rich apoptotic adipocytes, a process critical to understanding chronic inflammation in obesity and metabolic disease. The density disparity between macrophages, which sink and adhere to culture surfaces, and adipocytes, which float due to their lipid content, has prevented conventional co-culture approaches from achieving sustained cell-cell contact. To address this challenge, we developed a microfluidic system that confines adipocytes and lipid droplets in close proximity to macrophages. This platform features recessed micro-traps within the upper surface of a microfluidic chamber that trap buoyant objects while allowing media exchange and delivery of reagents for live-cell and immunofluorescence imaging. Time lapse imaging revealed that the dynamic process of macrophages-dead corpse interactions, showing that individual macrophages cannot engulf entire corpses but instead mechanically deform them. Furthermore, the platform successfully recapitulates the formation of Crown-Like Structures (CLS), clusters of macrophages surrounding dead adipocytes that are hallmarks of adipose tissue inflammation. Long-term culture revealed that CLS effectively clear lipids compared to partial macrophage engagement, providing mechanistic insights that were previously unattainable with standard histological approaches. Beyond the macrophage-lipid interaction, this platform has potential for studying interactions between adherent cells and buoyant targets, such as microplastics, opening new avenues for research where density mismatch poses a major barrier.