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bioRxiv · 10.1101/2020.09.04.283184

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

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.
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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 template1. Centriole assemble from likewise symmetrical ring polymers of SAS-6 proteins, orthogonal to a toroidal surface surrounding the resident centriole2-4. 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.

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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.. 2020-09-04. Surface-catalyzed SAS-6 self-assembly directs centriole formation through kinetic and structural mechanisms. https://doi.org/10.1101/2020.09.04.283184

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