Speaker: Stylianos Varchanis, Ph.D., Flatiron Research Fellow – Biophysical Modeling
Deciphering the Biomechanical Origins of Centrosome Centering and Decentering in Microtubule Asters
Asters are radial arrays of microtubules (MTs) organized by the centrosome in dividing eukaryotic cells and are essential for spindle positioning, pronuclear migration, and cell organization. To elucidate the mechanisms governing centrosome centering and decentering, we develop a biophysical model of intracellular aster transport that captures MT growth, elastic bending, motor-driven forces, interfacial sliding, and hydrodynamic drag. The aster is modeled as a dense bed of flexible, inextensible fibers anchored to a rigid centrosome and immersed in a confined Stokes fluid. Using stabilized finite element simulations, we construct phase diagrams and identify the dominant biomechanical pathways underlying centrosome dynamics.
Speaker: Mahsa Mofidi, Ph.D., Flatiron Research Fellow – Structural & Molecular Biophysics
Looking Closer at Tubulin Interactions and C-Terminal Tail Dynamics in the Microtubule Lattice
Microtubules are dynamic cytoskeletal polymers whose lattice mechanics and surface chemistry are central to intracellular transport, neuronal integrity, and mitosis. Their behavior emerges from the complex interplay among tubulin subunits, nucleotide state, lattice architecture, and associated proteins; yet, the molecular determinants governing these interactions remain incompletely understood. Using all-atom molecular dynamics simulations of GDP-bound microtubules, I investigate lateral and longitudinal interactions between tubulin subunits within the microtubule lattice. I further compare how α- and β-tubulin C-terminal tails (CTTs), which are dynamic, negatively charged, and intrinsically disordered regions, interact with neighboring tubulins. Consistent with previous cryo-EM findings, the α-CTT preferentially interacts with basic residues on β-tubulin. We find that both α- and β-CTTs favor interactions oriented toward the microtubule minus end: the α-CTT preferentially interacts with the β-tubulin in the neighboring dimer in the minus-end direction, whereas the β-CTT predominantly docks onto Lys of α-tubulin. β-CTTs are more solvent accessible, while α-CTTs form more persistent interactions with their own and neighboring tubulin subunits. Together, these findings reveal distinct docking modes for α- and β-tubulin CTTs and show how atomistic simulations can bridge experimental observations with molecular mechanisms.