How Can We Reliably Highlight Nanoscale Lipid Heterogeneities in Erythrocyte Membranes?

Abstract This study explores atomic force microscopy-infrared spectroscopy (AFM-IR) to characterize red blood cells (RBC) affected by Gaucher disease (GD). Conventional mass spectrometry and vibrational spectroscopy lack the spatial resolution to probe lipid distribution at the nanoscale, justifying the use of AFM-IR. An optimized analytical workflow was developed, ensuring the chemical and morphological stability of RBC samples. Comparative analyses between healthy (CTL) and GD RBCs reveal disease-specific biochemical alterations, notably nanoscale heterogeneity in lipid and/or protein distributions. These findings establish AFM-IR as a powerful tool for high-resolution molecular mapping of pathological erythrocytes.