Design and self-assembly of cytomotive filaments

Cytomotive filaments, a prominent class of cytoskeletal polymers comprising the actin and tubulin families, combine directional growth with monomer turnover to perform essential cellular functions. While the functional role of turnover is becoming increasingly clear, how these filaments dynamically self-assemble using a single monomer type remains an open question. Here we exploit physical modelling in combination with genetic algorithms to elucidate the design principles that drive monomer self-assembly into treadmilling filaments - polar filaments that grow on one end and shrink on the other. We first show that directional polymer growth is only possible when a structurally polar monomer changes conformation upon polymerisation, and identify three different mechanisms through which the structural polarity of a monomer can induce kinetic polarity. We then prove that to prevent filament fragmentation and promote end depolymerisation upon nucleotide hydrolysis, the conformation change of a polar monomer must involve both its interface-forming sites. Combining these results, we identify the principles required to design treadmilling monomers, and showcase the emergence of treadmilling dynamics from the bottom-up. Our work sheds light on the physical mechanisms underlying cytomotive self-assembly of biological polymers, and lays the base for the realization of essential cytoskeletal features in synthetic systems with programmable building blocks.