A groundbreaking study led by André Nadler and Alf Honigmann at the Max Planck Institute for Cell Biology and Genetics (MPI-CBG) and the Biotechnology Center (BIOTEC) in Dresden has unveiled new insights into how cells manage lipid transport. The research team, which includes experts from multiple institutions, has developed a novel chemical labeling strategy that overcomes previous imaging limitations, enabling them to create the first quantitative map of lipid movement within cells.
Material Ph.D. student Kristin Böhlig was key in this work, combining her expertise in synthetic organic chemistry to make modified lipids. These lipids, modified with a handful of different atoms, were produced to be easily monitored by fluorescence microscopy. This breakthrough allowed scientists to follow lipids to see exactly where they go and what they do over time. This allowed them to obtain a global perspective on lipid trafficking between cell membranes and organelle membranes.
The resulting study, published in Nature, was the result of nearly five years of work. Böhlig noted the significance of the project, stating, “We started our project with synthesizing a set of minimally modified lipids that represent the main lipids present in organelle membranes.” This groundwork made a strong visual foundation for the teams’ cutting-edge imaging approaches.
Juan M. Iglesias-Artola created an image analysis pipeline. It uses computer technology to apply an AI-powered method of automating distinct image segmentation that offers strong backing for their conclusion. This system allows for spatiotemporal quantification of lipid traffic between cellular organelles. “To address our specific needs, I developed an image analysis pipeline with automated image segmentation assisted by artificial intelligence to quantify the lipid flow through the cellular organelle system,” Iglesias-Artola explained.
The team’s surprising findings demonstrate that carrier proteins orchestrate 85% to 95% of lipid traffic across membrane-bound cell organelles. These proteins transport lipids at speeds that are an order of magnitude faster than vesicle-based lipid transport. This short and storied transport route is essential to the preservation of cellular homeostasis. Perhaps most importantly, it will inform our understanding of metabolic and neurodegenerative disease that occur when lipid homeostasis is lost.
Nadler emphasized the challenges faced during the project, stating, “Imaging lipids in cells has always been one of the most challenging aspects of microscopy… we quickly decided to go for it.” He understood that the ability to incorporate artificial intelligence made their data analysis significantly more powerful. He said at the time, “Looking back, the delay was a good thing.”
Honigmann highlighted the breakthrough nature of their imaging technique: “Our lipid-imaging technique enables mechanistic analysis of lipid transport and function directly in cells, which has been impossible before.” This advancement creates a whole new world of studying what lipids do inside cells.
The collaborative research team included specialists from rural and urban institutions. Particularly important were contributions by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the J. Heyrovsky Institute of Physical Chemistry in Prague. Mathematical modeling efforts by Björn Drobot provided valuable insights to lipid transport dynamics.