Transmembrane transport of multicomponent liposome-nanoparticles into giant vesicles

With the emergence and rapid development of nanotechnology,the nanoparticles hybridized with multicomponent lipids are more and more used in gene delivery.These vectors interact with the cell membrane before entering into the cell.Therefore,the nature of this interaction is important in investigating multicomponent liposome-nanoparticle(MLP)transport across the cell membrane.In this paper the transport of MLPs across the membranes of giant vesicles(GVs)in solvents is studied by using the self-consistent field theory(SCFT).Based on the analysis of the MLP permeating the GV membranes,a simple transport model is proposed.The effects of the difference in membrane morphology and the size of the nanoparticle on the endocytosis are discussed systematically.The role of energy barriers in quasi-equilibrium is also examined.The results indicate that the interaction between MLP and GV is a spontaneous process and the energy barrier needs overcoming to form metastable intermediates.The results provide theoretical reference for better understanding the transmembrane transport process of nanoparticles,and guidance for relevant experimental studies as well.

Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force.However,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive.In this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis,molecular dynamics simulations,and live cell assays.The results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming concentration.Moreover,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane tension.Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin’s ability to induce pore formation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL^(-1)melittin.Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.