Abstract 

Discovering the physical principles directing organelle assembly is a fundamental pursuit in biophysics. Centrioles are evolutionarily conserved organelles with a signature 9-fold rotational symmetry of chiral microtubules imparted onto the cilia they template. Centriole assemble from likewise symmetrical ring polymers of SAS-6 proteins, orthogonal to a toroidal surface surrounding the resident centriole. How surface properties ensure ring assembly with proper symmetry and orthogonal arrangement is not known. Here, we deploy a combination of high speed atomic force microscopy (HS-AFM) and machine learning to decipher the physical principles of SAS-6 self-assembly dynamics. We demonstrate that surface-guided SAS-6 self-assembly is a coagulation-fragmentation system, with dynamic ring opening and closing being critical for robust generation of 9-fold symmetrical rings. Moreover, by determining the effective dissociation constant of the system, we discovered that the surface catalyses SAS-6 self-assembly, shifting the equilibrium ~10^4 fold compared to solution. Moreover, molecular dynamics and HS-AFM revealed that the surface converts helical SAS-6 polymers into 9-fold ring polymers with residual asymmetry, which may impart chiral features to centrioles and cilia. Overall, we discovered two fundamental physical principles directing robust centriole organelle assembly.