Spatiotemporal Insights into Caveolae Function: Live Cell Tracking of Caveolae Endocytosis & Lipid Internalization

• Applicant: Professorin Dr. Claudia Matthäus
• Subject Area: Biophysics
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575200544

The controlled uptake of lipids is fundamental to cellular energy balance and metabolic regulation. Caveolae—specialized, bulb-shaped plasma membrane invaginations (60–100 nm)—are known to mediate lipid uptake and endocytosis in adipocytes, muscle, and endothelial cells. While their structural composition, involving caveolin1 and cavin proteins, is well-characterized, the molecular regulation of caveolae-mediated lipid uptake and subsequent trafficking remains largely unresolved. In particular, it is unclear how extracellular lipids influence caveolar dynamics and cellular uptake, and how caveolae vesicles migrate to lipid droplets within the cytosol. This project addresses this knowledge gap by implementing a novel imaging and analysis pipeline combining TIRF microscopy, fluorescence correlation spectroscopy (FCS), and super-resolution STED microscopy to detect and track single caveolae in live cells in real time. Based on our preliminary data and custom analysis tools, we propose a systematic analysis of caveolae dynamics across three major aims: (1) Characterize caveolae formation and mobility at the plasma membrane upon lipid stimulation, (2) Quantify individual caveolar endocytic events using advanced live-cell imaging strategies, (3) Track the intracellular trafficking of caveolae to lipid droplets in four-dimensional space using volumetric microscopy. By combining state-of-the-art imaging with automated analysis, this project enables high-resolution investigation of caveolae behavior at the single-organelle level. The expected findings will provide a mechanistic understanding of caveolae mediated lipid uptake and intracellular trafficking, offering new insights into the organization of the plasma membrane, caveolae dynamics and lipid trafficking. In the long term, this research will contribute to the broader understanding of caveolae biology and may lay the basis for future translational approaches targeting metabolic and cardiovascular diseases linked to dysregulated lipid homeostasis.

• DFG Programme: Research Grants