Nanodissected elastically loaded clathrin lattices relax to increased curvature

Clathrin-mediated endocytosis (CME) is the major endocytosis pathway for the specific internalization of large compounds, growth factors, and receptors. Formation of internalized vesicles from the flat plasma membrane is accompanied by maturation of cytoplasmic clathrin coats. How clathrin coats mature and the mechanistic role of clathrin coats are still largely unknown. Maturation models proposed clathrin coats to mature at constant radius or constant area, driven by molecular actions or elastic energy. Here, combining high-speed atomic force microscopy (HS-AFM) imaging, HS-AFM nanodissection, and elasticity theory, we show that clathrin lattices deviating from the intrinsic curvature of clathrin form elastically loaded assemblies. Upon nanodissection of the clathrin network, the stored elastic energy in these lattices drives lattice relaxation to accommodate an ideal area-curvature ratio toward the formation of closed clathrin-coated vesicles. Our work supports that the release of elastic energy stored in curvature-frustrated clathrin lattices could play a major role in CME.