Molecular probes for tracking lipid droplet membrane dynamics

Lingxiu Kong, Qingjie Bai, Cuicui Li, Qiqin Wang, Yanfeng Wang, Xintian Shao, Yongchun Wei, Jiarao Sun, Zhenjie Yu, Junling Yin, Bin Shi, Hongbao Fang, Xiaoyuan Chen () and Qixin Chen ()
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Lingxiu Kong: Shandong First Medical University & Shandong Academy of Medical Sciences
Qingjie Bai: Shandong First Medical University & Shandong Academy of Medical Sciences
Cuicui Li: National University of Singapore
Qiqin Wang: Shandong First Medical University & Shandong Academy of Medical Sciences
Yanfeng Wang: Shandong First Medical University & Shandong Academy of Medical Sciences
Xintian Shao: Shandong First Medical University & Shandong Academy of Medical Sciences
Yongchun Wei: Shandong First Medical University & Shandong Academy of Medical Sciences
Jiarao Sun: Shandong First Medical University & Shandong Academy of Medical Sciences
Zhenjie Yu: Shandong First Medical University & Shandong Academy of Medical Sciences
Junling Yin: Shandong First Medical University & Shandong Academy of Medical Sciences
Bin Shi: Shandong First Medical University & Shandong Academy of Medical Sciences
Hongbao Fang: Nanjing Normal University
Xiaoyuan Chen: National University of Singapore
Qixin Chen: Shandong First Medical University & Shandong Academy of Medical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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− 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.

Date: 2024
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DOI: 10.1038/s41467-024-53667-7

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