The study investigates the receptor-independent mechanism of internalization of the third helix of the Antennapedia homeodomain, a Drosophila transcription factor. The authors found that a 16-amino acid peptide corresponding to this helix can be internalized by cells in culture at both 4°C and 37°C, suggesting a receptor-independent mechanism. They demonstrated that the α-helical structure is not essential for internalization, as peptides with prolines introduced did not hinder internalization. The peptides were visualized using confocal microscopy and electron microscopy, showing their presence in the cytoplasm and nucleus. The results indicate that the internalization process may involve direct interactions with membrane phospholipids, potentially through the formation of inverted micelles. This finding has implications for the development of cellular vectors for delivering biologically active substances into cells.The study investigates the receptor-independent mechanism of internalization of the third helix of the Antennapedia homeodomain, a Drosophila transcription factor. The authors found that a 16-amino acid peptide corresponding to this helix can be internalized by cells in culture at both 4°C and 37°C, suggesting a receptor-independent mechanism. They demonstrated that the α-helical structure is not essential for internalization, as peptides with prolines introduced did not hinder internalization. The peptides were visualized using confocal microscopy and electron microscopy, showing their presence in the cytoplasm and nucleus. The results indicate that the internalization process may involve direct interactions with membrane phospholipids, potentially through the formation of inverted micelles. This finding has implications for the development of cellular vectors for delivering biologically active substances into cells.