Cellular dry mass and volume dynamics in methamphetamine-induced apoptosis determined by label-free quantitative phase imaging

Objectives To determine how methamphetamine-induced apoptosis alters cellular dry mass and volume, and to evaluate whether quantitative phase imaging (QPI) techniques, specifically transport of intensity equation (TIE) imaging and optical diffraction tomography (ODT), can non-invasively quantify these biophysical changes in cultured C6 cells. Methods C6 glial cells were exposed to increasing concentrations of methamphetamine and imaged over time using TIE-based QPI to measure dry mass dynamics. Complementary measurements of both dry mass and cell volume were obtained using ODT. Dose-response and time-course analyses were performed to characterize biophysical signatures associated with methamphetamine-induced apoptosis. Results TIE imaging revealed dose-dependent and time-dependent alterations in cellular dry mass during methamphetamine exposure. ODT measurements demonstrated a concurrent decrease in cell volume and an increase in dry mass, consistent with hallmark apoptotic shrinkage. The combined QPI modalities provided internally consistent, label-free quantification of biophysical remodeling during methamphetamine-triggered cell death. Conclusions Label-free QPI enables robust, non-invasive measurement of dry mass and volume changes during methamphetamine-induced apoptosis. The observed coupling of volume loss with dry mass accumulation provides new insight into the biophysical progression of neuronal cell death and establishes QPI as a powerful tool for studying neurotoxic mechanisms.