Single-Mode Fiber Image Relay Mass Spectrometry Imaging Reveals Lipid Heterogeneity during Drug-Induced Apoptosis

Area of Science:

• Biochemistry
• Cell Biology
• Analytical Chemistry

Background:

• Cellular lipid heterogeneity significantly impacts cell phenotypes and metabolic functions.
• High-spatial-resolution mass spectrometry imaging (MSI) is essential for studying single-cell lipid variations.
• Existing MSI techniques may face limitations in deployment and resolution.

Purpose of the Study:

• To develop and validate a novel, user-friendly, single-mode fiber MSI platform with submicrometer resolution.
• To visualize and quantify lipid distributions at the single-cell level in biological samples.
• To investigate lipid remodeling during drug-induced apoptosis and understand metabolic reprogramming.

Main Methods:

• Development of a deployable single-mode fiber image relay MSI platform with ~800 nm spatial resolution.
• Integration of plasmonic gold nanoparticles (AuNPs) for enhanced signal detection.
• Application of the platform for lipid profiling in mouse brains and individual HeLa/HepG2 cells.
• Quantification of lipid remodeling during emodin-induced apoptosis in HeLa cells.

Main Results:

• Successful visualization of diverse lipid distributions in mouse brains and individual cells.
• Demonstration of cell-phenotype-specific lipid profiling capabilities.
• Quantification of dose- and time-dependent lipid remodeling during emodin-induced apoptosis.
• Identification of progressive, network-mediated metabolic reprogramming distinct from acute collapse.
• Observation of suppressed structural phospholipids and mobilized energy reserves during emodin treatment.
• Revealed mechanism-dependent lipid fingerprints and significant single-cell heterogeneity across cell types and drugs.

Conclusions:

• The developed MSI platform provides an accessible method for studying lipid metabolism at single-cell resolution.
• Emodin-induced apoptosis involves a distinct metabolic reprogramming pathway characterized by lipid remodeling.
• The findings highlight the importance of single-cell lipid heterogeneity in understanding cellular responses to stimuli and disease.