Dynamics of spontaneous wrapping of microparticles by floppy lipid membranes

Wrapping Pathways of Anisotropic Dumbbell Particles by Giant Unilamellar Vesicles

“…The latter is often exploited by viruses for cell entry and proliferation and key to nanomedical applications such as drug delivery and imaging . To single out receptor-mediated effects from active mechanisms involved in the engulfment, simplified passive model systems can be employed, which recently led to a conclusive understanding of the wrapping of spherical objects. , However, biological objects such as bacteria and viruses ,, as well as nanoparticles relevant for applications in nanomedicine but also nanotoxicology often possess nonspherical shapes. Moreover, in vitro experiments with nanoparticles and simulations have shown that the size and shape influence their likelihood to be taken up by endocytosis. ,− …”

“…The wrapping pathways of spheres at sufficiently low membrane tensions have been shown to be a continuous transition from attached to fully wrapped, occurring either spontaneously or after activation. ,, In contrast, anisotropic particles such as ellipsoids and rods are expected to reorient during the wrapping process or become trapped in metastable states due to their varying curvature. − The aspect ratio of these particles as well as the degree of rounding of their tip were the key parameters affecting the wrapping orientation with respect to the membrane and their metastable and stable states. , Despite the extensive work in theory and simulations and exciting observations on shape-dependence in phagocytosis, no experimental work has investigated the passive wrapping process of anisotropic particles by lipid membranes and tested these predictions yet.…”

“…Subsequently, its CoM moves inward to almost d ≈ 1.5 d s from the undisturbed membrane contour, before returning to a more parallel orientation and an insertion depth about d ≈ 0.7 d s . This overshooting and recoil is similar to that observed for spheres previously. , If the dumbbell initially is roughly perpendicular the membrane, then it first becomes oriented more precisely perpendicular until it is covered halfway ( d = 0 and θ ≈ 10°) before being wrapped further and finally ending in a more parallel orientation at a similar distance from the undisturbed membrane as the initially parallel dumbbells. Due to the spherical symmetry of the lobes, the point where the membrane peels off from the particle and makes a catenoid-shaped neck with the vesicle is not uniquely determined.…”

“…The comparison between the theoretical and experimental results allows us to estimate the membrane microviscosity, which is experimentally inaccessible. We find that our experimental measurements best fit the theoretical curves for a membrane microviscosity of η eff ≈ 0.8 Pa·s (Figure b), about 10 times larger than the lower bound estimated in ref . However, the theory in ref consistently overestimated the wrapping speed as compared with experiments on spheres, so it could be that the experiment microviscosity was larger than their theoretically predicted value.…”

“…However, the range of tensions we could replicate in experiments and simulations was quite limited. To be able to fully explore this effect, we extended a previously developed analytical theory describing the time to wrap colloids, , which was recently experimentally confirmed, and adapted it to the shape of a dumbbell (details of the theory can be found in the SI). In doing so we could explore the effect of tension on time to wrap the dumbbell for a range of theoretical parameters.…”