Hierarchical Quatsome-RGD Nanoarchitectonic Surfaces for Enhanced Integrin-Mediated Cell Adhesion

• Published in: ACS applied materials & interfaces 2022-10, Vol.14 (42), p.48179-48193
• Main Authors: Martínez-Miguel, Marc, Castellote-Borrell, Miquel, Köber, Mariana, Kyvik, Adriana R., Tomsen-Melero, Judit, Vargas-Nadal, Guillem, Muñoz, Jose, Pulido, Daniel, Cristóbal-Lecina, Edgar, Passemard, Solène, Royo, Miriam, Mas-Torrent, Marta, Veciana, Jaume, Giannotti, Marina I., Guasch, Judith, Ventosa, Nora, Ratera, Imma
• Format: Article
• Language: English
• Subjects: Surfaces, Interfaces, and Applications
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.2c10497

The synthesis and study of the tripeptide Arg-Gly-Asp (RGD), the binding site of different extracellular matrix proteins, e.g., fibronectin and vitronectin, has allowed the production of a wide range of cell adhesive surfaces. Although the surface density and spacing of the RGD peptide at the nanoscale have already shown a significant influence on cell adhesion, the impact of its hierarchical nanostructure is still rather unexplored. Accordingly, a versatile colloidal system named quatsomes, based on fluid nanovesicles formed by the self-assembling of cholesterol and surfactant molecules, has been devised as a novel template to achieve hierarchical nanostructures of the RGD peptide. To this end, RGD was anchored on the vesicle’s fluid membrane of quatsomes, and the RGD-functionalized nanovesicles were covalently anchored to planar gold surfaces, forming a state of quasi-suspension, through a long poly­(ethylene glycol) (PEG) chain with a thiol termination. An underlying self-assembled monolayer (SAM) of a shorter PEG was introduced for vesicle stabilization and to avoid unspecific cell adhesion. In comparison with substrates featuring a homogeneous distribution of RGD peptides, the resulting hierarchical nanoarchitectonic dramatically enhanced cell adhesion, despite lower overall RGD molecules on the surface. The new versatile platform was thoroughly characterized using a multitechnique approach, proving its enhanced performance. These findings open new methods for the hierarchical immobilization of biomolecules on surfaces using quatsomes as a robust and novel tissue engineering strategy.