Lattice-Lightsheet-Microscope

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581768723

Understanding how cells sense, generate, and transmit mechanical forces is key to figuring out how tissues grow, adapt, and fail in health and disease. Our work focuses on mechanically probing cells and tissues, from intracellular transport all the way to organ-scale function, using elastic microprobes, traction force microscopy, optical tweezers, and active microrheology. While we can currently map forces and viscoelastic properties in large 3D systems, we hit a wall at smaller scales. Conventional spinning-disk or multiview light-sheet microscopy can't deliver fast, near-isotropic 3D imaging without frying living cells or losing spatial detail. To break this barrier, we request a Lattice Light-Sheet Microscope. Its ultra-gentle illumination and almost isotropic resolution enable fast, long-term 3D imaging deep inside cells — something no other system here can do. This microscope will let us quantify intracellular stresses by tracking deformations of soft hydrogel beads engulfed by cells, revealing mechanical cues guiding cargo transport and organelle positioning. We'll also investigate nuclear mechanics in contracting cardiomyocytes, connecting mechanical load to nuclear deformation and potential damage pathways relevant to cardiac hypertrophy. Finally, we’ll capture 3D dynamics of organelles, condensates, and lipid droplets to link cytoplasmic rheology with cell structure and function over time. The instrument will directly support CRC proposals (Mathematics Meets Measurement), ongoing RTG projects on intracellular mechanics (CYTAC), and collaborations in biology and medicine. It fills a unique gap in the Göttingen imaging landscape, unlocking high-speed 4D mechanobiology with minimal phototoxicity. By enabling force-inference microscopy inside living cells, this system will push mechanobiology into a regime where molecular function, organelle dynamics, and cellular mechanics finally meet in 3D and real time.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Lattice-Lightsheet-Mikroskop
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)
• Applicant Institution: Georg-August-Universität Göttingen
• Leader: Professor Dr. Timo Betz