Polylysines have been frequently used in drug delivery and antimicrobial and cell adhesion studies. Because of steric hindrance, chirality plays a major role in the functional difference between poly-L-lysine (PLL) and poly-D-lysine (PDL), especially when they interact with the plasma membranes of mammalian cells. Therefore, it is speculated that the interaction between chiral polylysines and the plasma membrane may cause different cellular behaviors. Here, we carefully investigated the interaction pattern of PLL and PDL with plasma membranes. We found that PDL could be anchored onto the plasma membrane and interact with the membrane lipids, leading to the rapid morphological change and death of A549 cells (a human lung cancer cell line) and HPAEpiCs (a human pulmonary alveolar epithelial cell line). In contrast, PLL exhibited good cytocompatibility and was not anchored onto the plasma membranes of these cells. Unlike PLL, PDL could trigger protective autophagy to prevent cells in a certain degree, and the PDL-caused cell death occurred via intense necrosis (featured by increased intracellular Ca 2+ content and plasma membrane disruption). In addition, it was found that the short-chain PDL with a repeat unit number of 9 (termed DL9) could locate in lysosomes and induce autophagy at high concentrations, but it could not elicit drastic cell death, which proved that the repeat unit number of polylysine could affect its cellular action. This research confirms that the interaction between chiral polylysines and the plasma membrane can induce autophagy and intense necrosis, which provides guidance for the future studies of chiral molecules/ drugs.

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 μg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field.