2026/01/07 by Marija Krstic, Christian Vanhille-Campos, Buzz Baum +2 · 1 voice
Engineering · Biochemistry, Genetics and Molecular Biology · #Advanced Materials and Mechanics #Cellular Mechanics and Interactions #Microtubule and mitosis dynamics
paper · doi:10.64898/2026.01.07.698144
openalex publication_date 2026/01/07 · openalex created_date 2026/01/08 · openalex updated_date 2026/07/22
Cytomotive filaments such as actin and FtsZ exhibit treadmilling, a turnover mode in which subunits are added at one end and removed from the other, driven by nucleotide hydrolysis. This dynamics, which requires directional filament growth and disassembly without fragmentation, is crucial for the function of these filaments. However, how treadmilling is encoded in the monomer properties remains unclear. Here we combine physical modelling with in silico evolution to identify the minimal monomer design principles that yield treadmilling. We show that directional growth requires a polymerization-induced change in the binding interface of the monomer. Fragmentation-free disassembly further requires that this conformational change allosterically couples two monomer interfaces that bind it to its left and right neighbours. Guided by these principles, we design a minimal particle-based monomer that spontaneously assembles into treadmilling filaments in simulations. This work establishes a physical framework for cytomotive filament dynamics and provides a foundation for engineering synthetic systems with controllable emerging treadmilling dynamics. Significance statement Treadmilling, the continuous, energy-driven assembly and disassembly of monomers at opposite ends of a filament, is a fundamental dynamic of the cytoskeleton across the tree of life. How can individual monomers self-assemble into a polar filament that grows at one end and shrinks at the other? By combining physical modelling and in silico evolution, we uncover the physical and geometrical principles that monomers must satisfy to naturally form treadmilling filaments. In particular, we show that polar assembly requires monomers to undergo a conformational change upon assembly. In turn, controlled filament disassembly requires this conformational change to geometrically couple a monomer’s two binding interfaces, preventing filament fragmentation. Our work provides a physical framework for designing functional self-assembling materials.