Lattice Light-Sheet Microscope (LLSM) for fast and gentle volumetric live cell imaging

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568484556

Understanding the complex, dynamic nature of cellular processes, their precise regulation, and mechanisms driving their dysregulation, ultimately leading to disease progression, is a central challenge in biomedical research. Cellular functions are orchestrated by highly coordinated molecular interactions, signaling pathways, and structural rearrangements occurring at multiple spatial and temporal scales. Advanced light microscopy techniques have revolutionized our ability to study these biological processes with exceptional spatial and temporal resolution. However, these methods often face significant limitations in live-cell imaging. Prolonged or intense light exposure, required for high-resolution imaging, induces phototoxicity and photobleaching, compromising image quality and disrupting the physiological processes by causing cellular stress. As a result, live-cell imaging has been limited by a trade-off between spatial and temporal resolution, imaging duration, and the preservation of biological integrity. Lattice Light-Sheet Microscopy (LLSM) addresses these challenges by enabling fast, high-resolution volumetric imaging with minimal photodamage. LLSM uses interfering Bessel beams to generate an ultra-thin structured light sheet, which is rapidly dithered to ensure uniform illumination and reduce artifacts. Unlike widefield or confocal microscopy, which continuously excite fluorophores throughout the sample, LLSM illuminates only the imaging plane. This selective illumination minimizes phototoxicity, preserves cell viability, and enables longer observation of sensitive biological structures. LLSM is ideally suited for studying dynamic processes in live cells, spheroids, and organoids under near-physiological conditions with subcellular resolution. It allows UDE researchers to investigate intracellular trafficking processes and the endo-lysosomal damage response, organelle homeostasis, cellular morphodynamics, and mitosis and cell cycle regulation across multiple time scales. Integration of photostimulation enhances LLSM’s functionality, enabling precise, spatially controlled light-induced perturbations such as acute cell stress (e.g. lysophagy, DNA damage) or light-induced protein degradation, followed by real-time imaging of the cellular response. Combination of high-speed volumetric imaging with targeted photomanipulation offers a powerful platform for dissecting the molecular mechanisms that drive cell fate decisions and disease progression. Incorporating LLSM into the ICCE Imaging Core Facility will provide UDE researchers with unparalleled live-cell imaging capabilities, accelerating new discoveries. By preserving physiological conditions while enabling high-resolution, high-speed imaging, LLSM will drive innovation in biomedical research and improve our understanding of the molecular mechanisms underlying disease progression.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Lattice Light-Sheet Mikroskop (LLSM) für schnelle und schonende volumetrische Lebendzelldarstellung
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)
• Applicant Institution: Universität Duisburg-Essen
• Leader: Dr. Nina Schulze