Vesicle internalization proceeds via a morphological phase transition

Area of Science:

• Cell Biology
• Biophysics
• Membrane Dynamics

Background:

• Vesicle internalization is crucial for endocytic transport and cellular compartmentalization.
• Energetics of vesicle budding and pearling depend on curvature, area asymmetry, and volume.
• Physical drivers of hemifused intermediate structural transformation are not fully understood.

Purpose of the Study:

• To investigate the physical principles governing structural transformations of hemifused intermediates during vesicle internalization.
• To identify and characterize morphological phase transitions in invaginating vesicles.

Main Methods:

• Utilized a continuum elastic model to simulate vesicle dynamics.
• Analyzed the energetic landscapes and morphological changes of hemifused vesicles.

Main Results:

• Identified a morphological phase transition from "eye" to "kettle" geometry in hemifused invaginating vesicles.
• This transition is discontinuous below a critical reduced volume threshold and continuous above it.
• Kettle morphology is metastable, suggesting a potential hysteretic externalization pathway.
• Increased spontaneous curvature or vesicle size can minimize free energy, but scaling vesicle size alone does not overcome the energy barrier.

Conclusions:

• The study quantitatively characterizes vesicle internalization intermediates, providing a structural reference for experimental imaging.
• The findings map the morphological evolution of internalization pathways across physical parameter space.
• Understanding these transitions is key to deciphering endocytic transport mechanisms.