Clathrin-coated membranes are precursors to coated vesicles in the rec
eptor-mediated endocytic pathway. In this paper we present a physical
model for the first steps of the transformation of a clathrin-coated m
embrane into a coated vesicle. The theory is based on in vitro cytopla
smic acidification experiments of Heuser (J. Cell Biol. 108:401-411) t
hat suggest the transformation proceeds by changes in the chemical env
ironment of the clathrin lattice, wherein the chemical environment det
ermines the amount of intrinsic, or spontaneous, curvature of the netw
ork. We show that a necessary step of the transformation, formation of
free pentagons in the clathin network, can proceed via dislocation un
binding, driven by changes in the spontaneous curvature. Dislocation u
nbinding is shown to favor formation of coated vesicles that are quite
small compared to those predicted by the current continuum theories,
which do not include the topology of the clathrin lattice.