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

Abstract

Fusion events in living cells are intricate phenomena that require the coordinate action of multicomponent protein complexes. However, simpler synthetic tools to control membrane fusion in artificial cells are highly desirable. Native membrane fusion machinery mediates fusion, driving a delicate balance of membrane curvature and tension between two closely apposed membranes. Here, we show that silica nanoparticles (SiO2 NPs) at a size close to the cross-over between tension-driven and curvature-driven interaction regimes initiate efficient fusion of biomimetic model membranes. Fusion efficiency and mechanisms are studied by Förster resonance energy transfer and confocal fluorescence microscopy. SiO2 NPs induce a slight increase in lipid packing likely to increase the lateral tension of the membrane. We observe a connection between membrane tension and fusion efficiency. Finally, real-time confocal fluorescence microscopy reveals three distinct mechanistic pathways for membrane fusion. SiO2 NPs show significant potential for inclusion in the synthetic biology toolkit for membrane remodeling and fusion in artificial cells.

Dynamics of asymmetric membranes and interleaflet coupling as intermediates in membrane fusion

“…Interestingly, the gentle membrane merging pathway, which represented a 35% of the total fusions between two DOPC GUVs recorded in our previous study (18) (Figure S1 b), is completely suppressed when one of the GUVs has a L o membrane. The reason for the absence of gentle merging membrane events is unclear.…”

“…S1 a). This value does not show statistically significant difference with respect to the proportion of fused GUVs observed in samples of just DOPC GUVs in isosmotic conditions (18) (Fig. S1 a).…”

“…From our results we did not see any preferential pathway with 35% of the fusions following the direct full fusion pathway, 30 % the hemifusion-fusion pathway and the remaining 35% undergoing gentle membrane merging (Figure S1 b). We proposed that the fusion pathway followed by the GUVs would be primarily determined by the membrane tension, so fusing GUVs that do not have enough tension to overcome the energy cost associated to the opening and expansion of a fusion pore would follow the gentle membrane merging pathway (18).…”

“…Previously, we showed that silica nanoparticles (SiO 2 NPs) of 30 nm diameter effectively mediate fusion of DOPC GUVs by imposing a balance between membrane curvature and increased lateral tension in the membranes (18). Here, we use the same type of SiO 2 NPs to mediate membrane fusion between L d and L o GUVs with the aim to generate phase separated GUVs.…”

Protein corona alters the mechanisms of interaction between silica nanoparticles and lipid vesicles

“…Here, as also observed by Zhang et al , 19 we only observe the rapid pore opening event and simultaneous wrinkling of the membrane as the membrane transitions from fluid to solid mechanics in a process akin to a first order phase transition. The BSA corona increases the size of these SNPs above the critical diameter for spontaneous wrapping, that for SNPs interacting with DOPC membranes has been estimated to be 25–40 nm, 19,21 making membrane bending more energetically favourable. Thus, the BSA corona on these SNPs modifies the interaction mechanism so the membrane now wraps the NPs and creates highly curved membrane structures, where gentle shrinkage of the GUVs is facilitated by nanoscale membrane pores.…”