Biology subjects

Schachter, I.

Publications and source records attributed to Schachter, I..

3 recordsLinked to original sources

bioRxiv2026

Vesicle Internalization Proceeds via a Morphological Phase Transition

Vesicle internalization proceeds through a series of multivesicular topologies essential for endocytic transport and cellular compartmentalization. The energetic landscapes of related transitions, including vesicle budding and pearling, are known to be governed by the coupling of spontaneous curvature, leaflet area asymmetry, and reduced volume. However, the physical principles driving the structural transformation of hemifused intermediates remain unresolved. Using a continuum elastic model, we identify a morphological phase transition in hemifused invaginating vesicles, from an initial lens-like geometry to an elongated "kettle" geometry. This transition is discontinuous as long as the invaginating vesicles reduced volume is below a critical threshold, but continuous otherwise. The kettle-like morphology is metastable across a broad range of leaflet area asymmetries, potentially enabling a hysteretic externalization pathway. Increasing either the spontaneous curvature of the shared outer leaflet or the size of the invaginating vesicle, alone or in tandem with the host vesicle, turns the kettle morphology into the global free energy minimum. Notably, simply scaling up the size of both vesicles does not eliminate the free energy barrier. This quantitative characterization provides a structural reference for identifying internalization intermediates witnessed in experimental imaging, and maps the morphological evolution of the internalization pathway across its physical parameter space.

biophysics↗

bioRxiv2026

Direct Membrane Penetration of Oligoarginines by Fluorescence and Cryo-electron Microscopy Combined with Molecular Simulations

Arginine-rich peptides are short amino acid chains capable of spontaneously crossing cellular membranes, with great potential for drug or other cargo delivery. Yet, the mechanisms underlying their cellular penetration are not fully understood. Here, we investigate the modes of action of nonaarginine (R9) across membranes of increasing compositional and biological complexity. We combine computational, fluorescence microscopy, and cryo-EM approaches to both visualize the membrane structural changes arising from peptide-lipid interactions and provide a molecular rationale for the observed effects. In large unilamellar vesicles, R9 binds preferentially to anionic and PE-rich membranes, induces lipid reorganization, and drives pronounced remodelling, including budding, bifurcations, and time-dependent formation of multilamellar stacks. In cell-derived extracellular vesicles, R9-induced remodelling is largely confined to bilamellar bifurcations. In live cells, fluorescent R9 forms surface puncta that precede cytosolic entry. Correlative cryo-fluorescence and electron tomography reveals that these puncta correspond to strongly folded, multilamellar membrane structures. We propose that these seemingly contrasting observations can be reconciled within a single R9 mechanism of action, involving membrane folding and stacking, where the different observed morphologies arise from the size of the accessible membrane reservoir.

biophysics↗

bioRxiv2024

Lipid Demixing Reduces Energy Barriers for High Curvature Vesicle Budding

Budding relies on membrane asymmetry, including composition, area, and osmotic differences, and involves large curvature changes in nanoscale lipid vesicles. So far, the combined impact of asymmetry and high curvatures on budding has remained unknown. Here, using continuum elastic theory, the budding pathway is detailed under realistic conditions. It shows that budding is less favored in smaller vesicles but lipid demixing can significantly reduce its energy barrier and yet high compositional deviations of more than 7% between the bud and vesicle only occur with phase separation on the bud.

biophysics↗