Plasma membrane vesicles preserve cell type specific physicochemical signatures

The plasma membrane encodes critical information about cellular identity and phenotype, yet detailed characterization of this complex interface remains technically challenging in whole cells. Giant plasma membrane vesicles (GPMVs), generated via chemically induced blebbing, offer a simplified yet biochemically rich model of the cell membrane. Here, we investigate whether GPMVs retain biophysical and biochemical properties reflective of their cell of origin. Using a panel of human cell lines - including microglial and four glioblastoma cell lines - we characterized both cells and their vesicles using fluorescence microscopy, atomic force microscopy (AFM), Fourier-transform infrared (FT-IR) spectroscopy, and principal component analysis (PCA). GPMVs preserved cell-line-specific stiffness ranking observed in AFM measurements, and notably, FT-IR spectra of GPMVs enabled discrimination between cell lines, unlike spectra from intact cells. Our results highlight GPMVs as faithful surrogates of native membranes and suggest their utility for biophysical phenotyping in health and disease.