Pixel-based AFM-IR uncovers nanoscale lipid remodeling in MPNST cells

Area of Science:

• Biophysics
• Cell Biology
• Cancer Research

Background:

• Malignant peripheral nerve sheath tumors (MPNST) display significant lipid organization changes, impacting tumor aggressiveness and radiotherapy resistance.
• Understanding these lipid alterations at the nanoscale is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate nanoscale lipid remodeling in Schwann and MPNST cells under cannabidiol (CBD) and ionizing radiation exposure.
• To introduce and validate a novel pixel-based atomic force microscopy-infrared spectroscopy (AFM-IR) semi-quantification framework for analyzing lipid organization.

Main Methods:

• Combined atomic force microscopy-infrared spectroscopy (AFM-IR) and fluorescence imaging to study lipid remodeling.
• Developed a pixel-based AFM-IR analysis strategy for semi-quantitative biochemical metrics.
• Utilized ANOVA with Tukey's post-hoc test for statistical comparison of lipid redistribution.

Main Results:

• Identified CBD- and irradiation-dependent modifications in phospholipids and cholesteryl esters using AFM-IR.
• The new AFM-IR framework revealed distinct nanoscale cholesteryl ester reorganization patterns in MPNST versus Schwann cells.
• AFM-IR spatial metrics correlated with fluorescence lipid droplet staining, validating the approach.

Conclusions:

• The developed pixel-based AFM-IR strategy enables robust nanoscale biochemical semi-quantification.
• This method effectively resolves lipid organization and remodeling in complex biological systems, differentiating responses in normal versus malignant cells.
• Findings highlight the potential of AFM-IR in understanding MPNST lipid dynamics and therapeutic responses.