Time-lapse high-dimensional super-resolution imaging of the late-stage division of two U2-OS cells [Zhanghao et al]

Despite the significant role of lipid membranes, approaches to study them in vivo have been limited. Lipid membranes surround most subcellular compartments and play an essential role in regulating the organelles’ biochemical functionalities. Now, a group of researchers has developed Spectrum and Polarization Optical Tomography (SPOT)—a technique to study the subcellular lipidomics in live cells. Observing the inner workings of structures (organelles) within cells, in real time, offers the promise of advancements in disease diagnosis and treatment.

The method, built off of earlier work on super-resolution polarization microscopy, is published in Nature Communications in the paper, “High-dimensional super-resolution imaging reveals heterogeneity and dynamics of subcellular lipid membranes.”

A lipid membrane’s “shape, composition, and phase synergistically regulate biophysical membrane properties, membrane protein function, and lipid-protein interactions,” noted Karl Zhangao, PhD, from UTS-SUSTech Joint Research Centre. “However it is challenging to observe such a level of complexity due to their similar chemical composition.”

Using just one dye that universally stains the lipid membranes, SPOT can simultaneously reveal lipid membrane morphology, polarity, and phase by measuring the intensity, spectrum, and polarization, respectively.

Combined with lipophilic probes, these high-throughput optical properties revealed lipid heterogeneities of ten subcellular compartments, at different developmental stages, and even within the same organelle. Furthermore, the researchers obtained real-time monitoring of the multi-organelle interactive activities of cell division. They also successfully observed the multi-organelle interactive activities of cell division, sophisticated lipid dynamics during the plasma membrane separation, tunneling nanotubules formation, and mitochondrial cristae dissociation.

“This is the first time researchers have been able to quantitatively study the lipid heterogeneity inside subcellular organelles,” said senior author Dayong Jin, PhD, director of UTS-SUStech Joint Research Centre and UTS Institute for Biomedical Materials and Devices.

“This is a very powerful tool for super-resolution imaging the inner working of each single cells, that will advance our knowledge in understanding how cells function, diagnose when a ‘factory’ or a transportation doesn’t work properly within the cell, and monitor the progression of disease,” Jin said

This work suggests research frontiers in correlating single-cell super-resolution lipidomics with multiplexed imaging of organelle interactome. “With such information, it isn’t too big a leap to identify pathways for potential drug treatments, as well as examine their efficacy right on the SPOT,” Jin said.

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