Clathrin polymerization exhibits high mechano-geometric sensitivity.

How tension modulates cellular transport has become a topic of interest in the recent past. However, the effect of tension on clathrin assembly and vesicle growth remains less understood. Here, we use the classical Helfrich theory to predict the energetic cost that clathrin is required to pay to remodel the 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 also to the instantaneous geometry of the membrane during shape evolution. Our study predicts a sharp reduction in clathrin coat size in the intermediate tension regime (0.01-0.1 mN m-1). 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 an 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.