Poly(Ionic Liquid) Nanoparticles Selectively Disrupt Biomembranes

Abstract

Polymer‐based nanoparticles have an increasing presence in research due to their attractive properties, such as flexible surface functionality design and the ability to scale up production. Poly(ionic liquid) (PIL) nanoparticles of size below 50 nm are very unique in terms of their high charge density and internal onion‐like morphology. The interaction between PIL nanoparticles and giant unilamellar vesicles (GUVs) of various surface charge densities is investigated. GUVs represent a convenient model system as they mimic the size and curvature of plasma membranes, while simultaneously offering direct visualization of the membrane response under the microscope. Incubating PIL nanoparticles with GUVs results in poration of the lipid membrane in a concentration‐ and charge‐dependent manner. A critical poration concentration of PILs is located and the interactions are found to be analogous to those of antimicrobial peptides. Microbial mimetic membranes are already affected at submicromolar PIL concentrations where contrast loss is observed due to sugar exchange across the membrane, while at high concentrations the collapse of vesicles is observed. Finally, a confocal microscopy–based approach assessing the particle permeation through the membrane is reported and a mechanism based on bilayer frustration and pore stabilization via particle integration in the membrane is proposed.

Characterization of lipid composition and diffusivity in OLA generated vesicles

“…The fluorescence in all cases scales as expected. Furthermore, the spread of our measurements falls within the error margins that have been reported for fluorescence calibration curves where known amounts of fluorescent dye were added to the membranes of electroformed vesicles [ 45 ]. These findings suggest that the lipid mixture in the OLA vesicles is not significantly affected by the difference in MW of the fluorophore.…”

Facile generation of giant unilamellar vesicles using polyacrylamide gels

“…For lamellarity quantification of GUVs, a single image was captured at the mid-plane of a number of seemingly unilamellar GUVs. We then adapted the methods described by Chiba et al 32 and Ewins et al 45 using the semi-automatic ImageJ plugin "Radial Profile Angle" 31 . Briefly, once a circular outline was chosen for each GUV, the algorithm integrated the signal around the complete circumference of the circle and reported an integrated intensity for the given radius.…”

Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles

“…If NPs get fully wrapped by the membrane, they can lead to fission processes through which they pull the membrane which engulfs them out from the GUV membrane. 41,42 These fission processes explain the fluorescence signal observed in the lumen of the GUVs in Figure 2a. A different mechanism is observed in Figure 2b, where the fusion occurs after the sudden breakage of the membrane at one end of the GUV contact region.…”

“…This enhanced localized fluorescence intensity is attributed to highly curved regions of the membrane induced by the NPs adhering to the GUV surface and being wrapped by the membrane. , The nanoscale membrane curvature induces an increased membrane area, and therefore number of fluorophores, per pixel in the x – y plane of the image, which translates into a brighter fluorescent signal. If NPs get fully wrapped by the membrane, they can lead to fission processes through which they pull the membrane which engulfs them out from the GUV membrane. , These fission processes explain the fluorescence signal observed in the lumen of the GUVs in Figure a. A different mechanism is observed in Figure b, where the fusion occurs after the sudden breakage of the membrane at one end of the GUV contact region.…”