Clathrin polymerization exhibits high mechano-geometric sensitivity

Abstract

How tension modulates cellular transport has become a topic of interest in the recent past. The effect of tension on clathrin assembly and vesicle growth continues to remain less understood. Here, we use the classical Helfrich theory to predict the energetic cost clathrin is required to pay to remodel membrane at different stages of vesicle formation. Our study reveals that this energetic cost is highly sensitive to not only the tension in the membrane but to the instantaneous geometry of the membrane during the shape evolution. Our study predicts a sharp reduction in clathrin coat size in the intermediate tension regime (0.01 − 0.1 mN/m). Remarkably, the natural propensity of the membrane to undergo bending beyond the Ω shape causes a significant decrease in the energy needed from clathrin to drive vesicle growth. Our studies in mammalian cells confirm a reduction in clathrin coat size in increased tension environment. In addition, our findings suggest that the two apparently distinct clathrin assembly modes, namely coated pits and coated plaques, observed in experimental investigations might be a consequence of varied tensions in the plasma membrane. Overall, the mechano-geometric sensitivity revealed in this study might also be at play during the polymerization of other membrane remodeling proteins.

The big and intricate dreams of little organelles: Embracing complexity in the study of membrane traffic

“…The requirement of actin dynamics to form a closed clathrin-coated bud shape in high-tension conditions provided support for two modeling studies that indicate that proteininduced snap-through instability can offset tension and drive CCP growth. 172,173 Further modeling revealed that energetic cost is sensitive to the geometry of membrane shape during vesicle formation 174 and confirmed experimental work that showed a reduction in CCP size at high tension. 171 Future modeling efforts should increasingly focus on multiscale approaches to integrate molecular dynamics simulation with continuum Monte-Carlo simulation to study proteinmembrane interactions in membrane trafficking processes.…”

Clathrin-mediated endocytosis regulates fMLP-mediated neutrophil polarization

“…Together, our analysis provides clear evidence that fMLP stimulation promotes nucleation of CCP and suggests the endocytic machineries signal to actin polymerization in neutrophil polarization. The observation of smaller CCPs is consistent with previous findings that cells with high tension have smaller CCPs [ 34 , 35 ] where we expect the leading edge of the cell to have higher membrane tension [36] . Previous work has demonstrated that receptor clustering can promote CCP nucleation [13] .…”

Gaussian curvature directs the distribution of spontaneous curvature on bilayer membrane necks

“…The requirement for two distinct mechanisms in two regions of neck radii could be related to the energy barrier that we found as the neck radius of the catenoid decreases. Other evidence of switch-like behaviors are found in endocytosis where multiple studies have reported the existence of a snap-through instability 35,[64][65][66] . Furthermore, soap films, with no bending rigidity, also exhibit a structural instability when held as catenoids 45,67 .…”