Long-Chain Poly-d-Lysines Interact with the Plasma Membrane and Induce Protective Autophagy and Intense Cell Necrosis

Abstract

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.

Poly-basic peptides and polymers as new drug candidate againstPlasmodium falciparum

“…Sulfated polyanions, especially heparin (Fig. 1A) , have been shown to inhibit the invasion of erythrocytes by merozoites ( 22, 26 ), with an IC50 for heparin noted as 11 µg/ml ( 22 ). To test the potential activity of polycationic peptides against P. falciparum parasites, we compared the activity of poly-L-lysine (PLL) and poly-L-ornithine with heparin and poly-L-glutamate in a single dose, 72 h in vitro treatment experiment (Fig.…”

Surface Modification Progress for PLGA-Based Cell Scaffolds

“…Furthermore, a high-molecular-weight (Mw) poly-L-lysine (27.4 kDa, 36.6 kDa) may affect the metabolic activity of cells and it has a specific cytotoxicity [ 99 ], which is related to the inhibition of mitochondrial function [ 100 ]. In addition, Wang et al [ 9 ] found that PDL could be anchored to the plasma membrane and interact with membrane lipids, which led to the rapid morphological change and death of A549 cells (a human lung cancer cell line), as well as HPAEpiCs (a human pulmonary alveolar epithelial cell line). However, PLL was not anchored to the plasma membranes of these cells and thus it exhibited good cytocompatibility.…”

“…Reprinted with permission from Ref. [ 9 ]. Copyright 2023, copyright America Chemical Society, Washington, DC, USA.…”

“…As a result, functional coatings have been applied on PLGA scaffolds to increase cell adhesion and viability. These coating materials include polymers such as polyethylene glycol (PEG) [ 7 ], polydopamine (PDA), polypyrrole (Ppy) [ 8 ], poly-lysine [ 9 ], polyethyleneimine (PEI) [ 10 ], and ECM components such as HA [ 11 ], laminin [ 12 ], FN [ 13 ], and collagen [ 14 ]. Studies have shown that modifying PLGA-based scaffolds with these materials could improve the hydrophilicity and cell adhesion on PLGA.…”

Chiral amino acid modified boron-dipyrromethene nanoparticles with different photodynamic activities

“…As the basic unit of life, amino acids are extremely important in the life process of organisms, such as the synthesis of protein and nucleotides, the production of adenosine triphosphate, and the maintenance of redox balance. 33–36 In this work, l / d -aspartic acid (Asp) modified BDP molecules (BDP-LAsp and BDP-DAsp) were synthesized. The modification of l -Asp and d -Asp is beneficial to increase the hydrophilicity of BDPs, so that they can self-assemble into nanoparticles (NPs) in water (Scheme 1a).…”