Supramolecular polymerisation of two-dimensional (2D) materials requires monomers with non-covalent binding motifs that can control the directionality of both dimensions of growth. A tug of war between these propagation forces can bias polymerisation in either direction, ultimately determining the structure and properties of the final 2D ensemble. Deconvolution of the assembly dynamics of 2D supramolecular systems has been widely overlooked, making monomer design largely empirical. It is thus key to define new design principles for suitable monomers that allow the control of the direction and the dynamics of two-dimensional self-assembled architectures. Here, we investigate the sequential assembly mechanism of new monolayer architectures of cyclic peptide nanotubes by computational simulations and synthesised peptide sequences with selected mutations. Rationally designed cyclic peptide scaffolds are shown to undergo hierarchical self-assembly and afford monolayers of supramolecular nanotubes. The particular geometry, the rigidity and the planar conformation of cyclic peptides of alternating chirality allow the orthogonal orientation of hydrophobic domains that define lateral supramolecular contacts, and ultimately direct the propagation of the monolayers of peptide nanotubes. A flexible 'tryptophan hinge' at the hydrophobic interface was found to allow lateral dynamic interactions between cyclic peptides and thus maintain the stability of the tubular monolayer structure. These results unfold the potential of cyclic peptide scaffolds for the rational design of supramolecular polymerisation processes and hierarchical self-assembly across the different dimensions of space.

Self-assembly of cyclic peptide monolayers by hydrophobic supramolecular hinges / I. Insua, A. Cardellini, S. Díaz, J. Bergueiro, R. Capelli, G.M. Pavan, J. Montenegro. - In: CHEMICAL SCIENCE. - ISSN 2041-6520. - 14:48(2023 Dec 13), pp. 14074-14081. [10.1039/d3sc03930g]

Self-assembly of cyclic peptide monolayers by hydrophobic supramolecular hinges

R. Capelli;
2023

Abstract

Supramolecular polymerisation of two-dimensional (2D) materials requires monomers with non-covalent binding motifs that can control the directionality of both dimensions of growth. A tug of war between these propagation forces can bias polymerisation in either direction, ultimately determining the structure and properties of the final 2D ensemble. Deconvolution of the assembly dynamics of 2D supramolecular systems has been widely overlooked, making monomer design largely empirical. It is thus key to define new design principles for suitable monomers that allow the control of the direction and the dynamics of two-dimensional self-assembled architectures. Here, we investigate the sequential assembly mechanism of new monolayer architectures of cyclic peptide nanotubes by computational simulations and synthesised peptide sequences with selected mutations. Rationally designed cyclic peptide scaffolds are shown to undergo hierarchical self-assembly and afford monolayers of supramolecular nanotubes. The particular geometry, the rigidity and the planar conformation of cyclic peptides of alternating chirality allow the orthogonal orientation of hydrophobic domains that define lateral supramolecular contacts, and ultimately direct the propagation of the monolayers of peptide nanotubes. A flexible 'tryptophan hinge' at the hydrophobic interface was found to allow lateral dynamic interactions between cyclic peptides and thus maintain the stability of the tubular monolayer structure. These results unfold the potential of cyclic peptide scaffolds for the rational design of supramolecular polymerisation processes and hierarchical self-assembly across the different dimensions of space.
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Settore CHIM/02 - Chimica Fisica
Settore FIS/03 - Fisica della Materia
   Peptide Dynamic Amphiphiles for Gene Therapy and Macromolecular Delivery
   TraffikGene
   European Commission
   Horizon 2020 Framework Programme
   838002

   Modeling approaches toward bioinspired dynamic materials
   DYNAPOL
   European Commission
   Horizon 2020 Framework Programme
   818776
13-dic-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1021048
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