Controlling lipid droplet dynamics via tether condensates

Abstract Lipid droplets (LDs) exhibit remarkable diversity and functionality within cells, depending on the metabolic needs of cells and the maintenance of lipid homeostasis. Such versatility is acquired through dynamic spatial and temporal positioning, enabling tight communication with other organelles. However, this complexity poses challenges in understanding LD biology. Controlled sequestration and release of LDs within their intracellular environment could offer a method to synchronize their behavior and better understand their function. Here, to advance in this direction, we developed ControLD (Controlled Trapping of Lipid Droplets), a novel approach designed to manipulate LDs and influence their dynamics and life cycle. By orchestrating the assembly/disassembly of engineered condensates, ControLD allows precise sequestration and release of LDs in cells. This technique effectively isolates LDs from the intracellular environment, drastically reducing interactions with other organelles. Notably, our experiments demonstrate that physically isolating LDs impairs their dynamics and remobilization during metabolic needs. ControLD represents a versatile tool for reversible LD trapping, with potential applications in controlling various cellular organelles.