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This study investigates the interaction between a cell membrane model composed of 1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (DPPS), a lipid commonly found on the outer surface of apoptotic cells, and patellamide, a cyclic peptide produced by the cyanobacterium Prochloron didemni, which has demonstrated cytotoxic activity against multidrug-resistant human leukemic cell lines. The effects of patellamide on DPPS monolayers were assessed using tensiometric, microscopic and spectroscopic techniques. Our results showed that the presence of 4% (v/v) patellamide induced a shift in the DPPS isotherm to lower molecular areas, indicating monolayer condensation. The compressibility modulus values decreased with patellamide, suggesting reduced rigidity of the monolayer. Hysteresis test did not reveal significant differences between the patellamide-containing and pure DPPS monolayers. Viscoelastic properties, measured using the oscillating barrier method, also showed minimal variation after patellamide addition. Surface potential measurements indicated a decrease in membrane potential upon drug incorporation. BAM images revealed the formation of interfacial aggregates for the monolayers containing patellamide, which were absent in pure DPPS. PM-IRRAS spectra showed an increase in the relative intensities of all peaks for the DPPS-patellamide system, although no new peaks or shifts in existing peaks were observed. Overall, these findings suggest that patellamide alters the physicochemical and structural properties of DPPS monolayers, potentially influencing membrane behavior in apoptotic cells and offering insights into its cytotoxic mechanism against multidrug-resistant leukemic cells.
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