No abstract

How nanoparticles interact with biomembranes is central for understanding their bioactivity. In this Letter, we report novel tubular membrane structures induced by adsorbed spherical nanoparticles, which we obtain from energy minimization. The membrane tubules enclose linear aggregates of particles and protrude into the vesicles. The high stability of the particle-filled tubules implies strongly attractive, membrane-mediated interactions between the particles. The tubular structures may provide a new route to encapsulate nanoparticles reversibly in vesicles.

The ESCRTs catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated ESCRT-III subunits Snf7, Vps24, and Vps2, and the AAA+ ATPase Vps4 such that membrane nanotubes reflecting the correct topology of scission could be pulled from giant vesicles. Upon ATP release by photo-uncaging, this system was capable of generating forces within the nanotubes in a manner dependent upon Vps4 catalytic activity and Vps4 coupling to the ESCRT-III proteins. Imaging of scission revealed Snf7 and Vps4 puncta within nanotubes whose presence followed ATP release, correlated with force generation and nanotube constriction, and preceded scission. These observations directly verify long-standing predictions that ATP-hydrolyzing assemblies of ESCRT-III and Vps4 sever membranes.

Maintaining a fluid bilayer is essential for cell signaling and survival. Lipid saturation is a key factor determining lipid packing and membrane fluidity, and it must be tightly controlled to guarantee organelle function and identity. A dedicated eukaryotic mechanism of lipid saturation sensing, however, remains elusive. Here we show that Mga2, a transcription factor conserved among fungi, acts as a lipid-packing sensor in the ER membrane to control the production of unsaturated fatty acids. Systematic mutagenesis, molecular dynamics simulations, and electron paramagnetic resonance spectroscopy identify a pivotal role of the oligomeric transmembrane helix (TMH) of Mga2 for intra-membrane sensing, and they show that the lipid environment controls the proteolytic activation of Mga2 by stabilizing alternative rotational orientations of the TMH region. This work establishes a eukaryotic strategy of lipid saturation sensing that differs significantly from the analogous bacterial mechanism relying on hydrophobic thickness.

Wrapping and internalization of nanoparticles by biomembranes play a critical role in drug delivery applications and nanomedicine. We study the wrapping process of a vesicle membrane around spherical and ellipsoidal nanoparticles via minimization of the bending and adhesion energies. We report two distinct regimes of spreading and internalization separated by an energy barrier and relate the success or failure of the internalization to the particle shape and wrapping orientation.We predict more difficult internalization for ellipsoidal particles with higher aspect ratios. Wrapping of ellipsoidal particles is associated with an orientational change of the particle. While the spreading starts on the flat side of the ellipsoidal particle, the particle changes its orientation during wrapping and the internalization is achieved in the tip orientation of both prolate and oblate ellipsoidal particles.