Self-assembly and nanomechanics of microtubules

Self-assembly plays a central role in producing ordered supramolecular structures. The crucial question is to identify the necessary features that a macromolecular monomer must have in order to form spontaneously a desired complex structure. We use molecular dynamics simulations to study the self-assembly of microtubules. The model monomer has a wedge-shape with binding sites on its lateral and vertical surface. We calculated a diagram of the self-assembled structures from these monomers. A modified Flory-Huggins theory was developed to explain the simulation results. We found that to form tubules the interaction strengths must be in a limited range where energy and entropy are in a delicate balance. In addition, helical tubules are frequently formed even though the initial design of the monomer is achiral. To enhance structural control of the self-assembly, we added chirality and a lock-and-key mechanism to the model monomer. As a result, we could control both the pitch and the number of protofilaments in the assembled tubules. We further investigate the nanomechanical response of microtubules under bending and indentation with the wedge model. Recently we extend our model to study the self-assembly of dimer building blocks, motivated by the fact that the subunit protein of microtubules is a tubulin dimer. Our ongoing work on atomistic modeling of tubulin proteins, microtubule segments, and the interactions between multivalent spermine ions and microtubules will also be presented.