Different pathways for engulfment and endocytosis of liquid droplets by nanovesicles

Abstract

During endocytosis of nanoparticles by cells, the cellular membranes engulf the particles, thereby forming a closed membrane neck that subsequently undergoes fission. For solid nanoparticles, these endocytic processes have been studied in some detail. Recently, such processes have also been found for liquid and condensate droplets, both in vitro and in vivo. These processes start with the spreading of the droplet onto the membrane followed by partial or complete engulfment of the droplet. Here, we use molecular dynamics simulations to study these processes at the nanoscale, for nano-sized droplets and vesicles. For both partial and complete engulfment, we observe two different endocytic pathways. Complete engulfment leads to a closed membrane neck which may be formed in a circular or strongly non-circular manner. A closed circular neck undergoes fission, thereby generating two nested daughter vesicles whereas a non-circular neck hinders the fission process. Likewise, partial engulfment of larger droplets leads to open membrane necks which can again have a circular or non-circular shape. Two key parameters identified here for these endocytic pathways are the transbilayer stress asymmetry of the vesicle membrane and the positive or negative line tension of the membrane-droplet contact line.

Remodeling of Biomembranes and Vesicles by Adhesion of Condensate Droplets

“…The mixture is modeled in terms of water (W) and solute (S) beads, both of which represent small molecular groups. For computational simplicity, the two types of beads are taken to have the same size and the interaction between two W beads is taken to be the same as the interaction between two S beads [ 29 , 30 , 50 ]. This symmetry implies that the phase diagram does not change when we substitute the W by the S beads and that this binary mixture has a particularly simple phase diagram as displayed in Figure 6 .…”

“…Partial engulfment of small condensate droplets by the membranes of nanovesicles has been observed in molecular dynamics simulations [ 30 ]. One example is shown in Figure 23 , which was obtained for solute mole fraction and solubility , corresponding to the two-phase coexistence region of the phase diagram in Figure 6 .…”

“…The process of stalled engulfment has been observed in molecular dynamics simulations as shown in Figure 24 [ 30 ]. In Figure 24 a, we see a stalled engulfment process that proceeds in an axisymmetric manner as can be concluded from the circular shape of the contact line between the interface and the vesicle membrane.…”

“…The contact line of a vesicle-droplet system represents the narrow membrane segment in contact with the liquid–liquid interface, which exerts capillary forces onto this line. The associated line tension can be positive or negative as revealed by molecular dynamics simulations [ 29 , 30 ]. Furthermore, the sign of the line tension determines the shape of narrow or closed membrane necks that are formed during the exocytosis or endocytosis of condensate droplets.…”

“…In contrast, for a positive line tension, the neck closes in an axisymmetric manner, which can then undergo membrane fission, thereby leading to the endocytosis and uptake of the adhering condensate droplet. For nanovesicles, the sign of the contact line tension is governed by stress asymmetry between the two leaflets of the bilayer membrane [ 30 ].…”