A new era in single-cell spectral analysis: Scientists achieve, for the first time, a real-time "spectral movie" of metabolic processes within living cells.
Release Time:
2025-12-24 15:18
In the life sciences, observing the chemical reactions inside a living cell is like trying to track the every breath and heartbeat of a specific pedestrian in a bustling city with a high-speed camera. Now, scientists have finally mastered this remarkable skill.
A recent landmark study published in the journal *Nature Methods* announced this breakthrough. An international team comprised of researchers from Stanford University, the Max Planck Institute for Biochemistry, and the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, successfully developed a novel imaging technique called "SCS-Movie." For the first time, it enables real-time, label-free, long-term observation of the dynamic changes of specific metabolic molecules inside a single living cell with millisecond resolution, bringing cell metabolism research from the era of "taking pictures" to the era of "making movies."
Key Technology: When Raman Scattering Meets "Exquisite Probes"
Traditional methods for observing cell metabolism, such as fluorescent labeling, require introducing exogenous dyes or gene-encoded fluorescent proteins into the cell. These "tags" may interfere with the cell's normal activities and are easily quenched, making long-term, in-situ tracking impossible. Another commonly used method, mass spectrometry, cannot perform dynamic observations while cells are alive.
The revolutionary nature of SCS-Movie technology lies in its ingenious integration of two cutting-edge technologies:
Stimulated Raman scattering microscopy: This is a label-free optical imaging technique. It uses two laser beams of specific wavelengths to simultaneously illuminate the sample. When the frequency difference between them matches the vibrational frequencies of intramolecular chemical bonds, a strong "stimulated Raman scattering" signal is generated. Different chemical bonds (such as C-H, C=O) have unique vibrational frequencies, so this technique can, like "molecular fingerprinting," directly "see" the distribution of major biomolecules such as lipids, proteins, and nucleic acids without adding any labels.
Metabolic activity probes: This is the team's independently developed "secret weapon." They designed a series of tiny, biocompatible "alkynyl" or "deuterated" small molecule probes. These probes are normally silent in the cellular spectral range, but once they are taken up by the cell and participate in specific metabolic pathways (such as newly synthesized DNA, proteins, or lipid droplets), they produce a unique and strong signal peak on the SRS spectrum, like a crisp snap of the fingers amidst the noisy background of metabolism.
“You can think of it this way,” explained Dr. Wei Zhang from Stanford University, the paper’s first author, “SRS provides a panoramic map of the entire cell, while our metabolic probes are the glowing, dynamically moving ‘target points’ on that map. By combining the two, we can track the complete journey of specific metabolites ‘from birth to death’ within the cell with unprecedented clarity and specificity.”
Stunning “Movies”: Revealing Unseen Details of Life Using SCS-Movie, the research team filmed several stunning “cellular metabolism movies”:
The “Life and Death Cycle” of Lipid Droplets: In a video lasting several hours, researchers clearly recorded the entire process inside an adipocyte, from the synthesis and growth of a single lipid droplet, to its fusion with other lipid droplets, and finally its decomposition and consumption. They even quantitatively measured the real-time changes in the unsaturation of triglycerides in the core of the lipid droplet during metabolism, something no previous technology could do.
Early Resistance to Cancer Cell Chemotherapy: In another experiment, the team observed the response of breast cancer cells within minutes of exposure to low-dose chemotherapy drugs. They discovered that some cells undergo dramatic and specific changes in protein synthesis activity and nucleotide metabolism spectral signals before any morphological changes or signs of death appear. This provides the earliest warning signal for identifying "refractory cells" that are about to develop drug resistance.
The "metabolic accompaniment" of neuronal activity: When a neuron is stimulated to generate an action potential, SCS-Movie captures synchronous fluctuations in specific lipid metabolism related to vesicle circulation and neurotransmitter synthesis near its synaptic terminal within milliseconds, visually revealing the precise coupling between electrical signals and metabolic activity.
Future prospects: Reshaping the paradigm of disease research and drug development
The potential of this technology goes far beyond a spectacle of basic science.
"It opens a window for us, allowing us to truly 'see' the origin and evolution of disease at the cellular metabolic level for the first time, rather than just observing the final result," said Li Chen, a researcher at the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and co-corresponding author of the paper.
This technology is expected to have a disruptive impact on the following areas:
Cancer research: Real-time tracking of the metabolic adaptation of tumor cells in the microenvironment, revealing the root causes of their drug resistance.
Neurodegenerative Diseases: Observing how the metabolism of surrounding cells is gradually "dragged down" during the accumulation of Tau protein or β-amyloid protein in an Alzheimer's disease model.
Immunology: Visualizing the metabolic reprogramming of T cells or macrophages in different states such as activation, functional execution, and exhaustion.
Drug Development: Real-time assessment of the impact of new drugs on target metabolic pathways at the cellular level, significantly improving screening efficiency and accuracy, and achieving "visualized drug efficacy assessment."
Industry Commentary: Professor David Sabatini, a leading expert in cell metabolism at Harvard University who was not involved in the study, commented: "This is a truly landmark tool in the field of metabolic research. It perfectly combines spatial omics and dynamic metabolomics, providing epoch-making depth of information and spatiotemporal resolution. It is foreseeable that within the next five years, all top metabolic laboratories will compete to adopt or develop similar technologies."
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