Fig. 1: Strategy used to prepare THD-based GTP-responsive ^CLNC_GTP/GTP*.

a Schematic illustrations of tubulin heterodimers (THDs) hybridized with GTP (THD_GTP), its nonhydrolysable analogue GTP* (THD_GTP*), and GDP (THD_GDP) at its β-tubulin unit. b Schematic illustration of two self-assembling modes of THD into microtubules (MTs). MT_GTP depolymerizes into THD_GDP upon GTP hydrolysis. THD_GDP rehybridizes with GTP after a GTP treatment, facilitating the formation of MT_GTP. In contrast, MT_GTP* does not undergo depolymerization. c Molecular structures of photoreactive molecular glues (\({{{\mathrm{Glue}}}}^{{{{\mathrm{CO}}}}_2-}\), \({{{\mathrm{Glue}}}}^{{{{{\mathrm{CO}}}}_{2}-}{\mathrm {Me}}}\), and Glue^FITC) bearing three guanidinium ions (Gu⁺) and benzophenone (BP) groups at their periphery and \({{{{\mathrm{CO}}}}_2-}\), CO₂ Me, and FITC groups at the focal core. d The molecular glue covalently binds to the protein surface at its photoexcited BP groups after the noncovalent adhesion via a Gu⁺/oxyanion multivalent salt-bridge interaction. e Schematic illustration of the multistep procedure for the synthesis of crosslinked nanocapsules (^CLNC_GTP/GTP*) from MT_GTP. MT_GTP is depolymerized into THD_GDP, which is incubated with a mixture of GTP* (83 mol%) and GTP (17 mol%) to form nanosheet NS_GTP/GTP*. Upon treatment with \({{{\mathrm{Glue}}}}^{{{{\mathrm{CO}}}}_2-}\), NS_GTP/GTP* is transformed into spherical nanocapsules (NC_GTP/GTP*), which are further exposed to UV light, affording ^CLNC_GTP/GTP*. Upon addition of GTP, ^CLNC_GTP/GTP* collapses through the conformational change of the THD units induced by GTP hydrolysis.