Peptide-mediated display of Tau-derived peptide for construction of microtubule superstructures

Microtubules are major cytoskeletons involved in various cellular functions, such as regulating cell shape and division and cargo transport <i>via</i> motor proteins. In addition to widely studied singlet microtubules, complex microtubule superstructures, including doublets and bundles, provide unique mechanical and functional properties <i>in vivo</i>. However, a method to construct such superstructures <i>in vitro</i> remains unresolved. This study presents a peptide-based approach for constructing microtubule superstructures by displaying Tau-derived peptides (TP) on the outer surface of microtubules using KA7 peptides as binding units. The KA7-connected TP (KA7-TP) bound to the <i>C</i>-terminal tail on the outer surface of microtubules and induced doublets and bundles by recruiting tubulin. Notably, the outer layers of the doublet microtubules generated by KA7-TP dissociated, highlighting the utility of this approach for studying the formation/dissociation mechanisms of microtubule superstructures. The simple peptide-based approach facilitates our understanding of microtubule superstructures and offers new opportunities for applying microtubule superstructures to nanotechnology.