Molecular probes for tracking lipid droplet membrane dynamics
Lipid droplets (LDs) feature a unique monolayer lipid membrane that has not been extensively studied due to the lack of suitable molecular probes that are able to distinguish this membrane from the LD lipid core. In this work, we present a three-pronged molecular probe design strategy that combines lipophilicity-based organelle targeting with microenvironment-dependent activation and design an LD membrane labeling pro-probe called LDM. Upon activation by the HClO/ClO<sup>-</sup> microenvironment that surrounds LDs, LDM pro-probe releases LDM-OH probe that binds to LD membrane proteins thus enabling visualization of the ring-like LD membrane. By utilizing LDM, we identify the dynamic mechanism of LD membrane contacts and their protein accumulation parameters. Taken together, LDM represents the first molecular probe for imaging LD membranes in live cells to the best of our knowledge, and represents an attractive tool for further investigations into the specific regulatory mechanisms with LD-related metabolism diseases and drug screening.
Authors
- Cuicui Li
- Qiqin Wang (ORCID: https://orcid.org/0000-0002-9169-5500)
- Hongbao Fang
- Xintian Shao (ORCID: https://orcid.org/0000-0001-7274-4947)
- Jiarao Sun
- Yongchun Wei
- Zhenjie Yu
- Lingxiu Kong
- Junling Yin (ORCID: https://orcid.org/0000-0002-0710-7674)
- Qingshun Bai (ORCID: https://orcid.org/0000-0002-8626-4431)
- Xiaoyuan Shawn Chen (ORCID: https://orcid.org/0000-0002-9622-0870)
- Yanfeng Wang
- Qixin Chen (ORCID: https://orcid.org/0000-0002-2998-5582)
- Bin Shi (ORCID: https://orcid.org/0000-0002-3643-9475)
Institutions
- Agency for Science, Technology and Research (SG)
- Nanjing Normal University (CN)
- Jinan University (CN)
- National University of Singapore (SG)
- Shandong First Medical University (CN)
- Clinical Nutrition Research Centre (SG)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1038/s41467-024-53667-7
- Citations
- 24
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 7.08
Funders
- National Research Foundation
- National University of Singapore
- National Natural Science Foundation of China
- Ministry of Education, India
- Natural Science Foundation of Shandong Province
- Medical Research Council
- National Medical Research Council