Surface-catalyzed SAS-6 self-assembly directs centriole formation through kinetic and structural mechanisms

Published: Sept. 4, 2020, 6:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.04.283184v1?rss=1 Authors: Banterle, N., Nievergelt, A. P., de Buhr, S., Hatzopoulos, G. N., Brillard, C., Andany, S., Hübscher, T., Sorgenfrei, F., Schwarz, U. S., Gräter, F., Fantner, G. E., Gönczy, P. Abstract: Discovering the physical principles directing organelle assembly is a fundamental pursuit in biology. Centrioles are evolutionarily conserved organelles with a 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 deployed photothermally-actuated off-resonance tapping high-speed atomic force microscopy (PORT-HS-AFM) to decipher physical principles of surface-guided SAS-6 self-assembly. Using machine learning to quantify the polymerization reaction and developing a coagulation-fragmentation model, we discovered that the surface shifts the reaction equilibrium by ~104 compared to the solution situation, explaining orthogonal organelle emergence. Moreover, molecular dynamics and PORT-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. Copy rights belong to original authors. Visit the link for more info