Hierarchically Multivalent Peptide–Nanoparticle Architectures: A Systematic Approach to Engineer Surface Adhesion

• Published in: Advanced science Vol. 9; no. 4; pp. e2103098 - n/a
• Main Authors: Jeong, Woo‐jin, Bu, Jiyoon, Jafari, Roya, Rehak, Pavel, Kubiatowicz, Luke J., Drelich, Adam J., Owen, Randall H., Nair, Ashita, Rawding, Piper A., Poellmann, Michael J., Hopkins, Caroline M., Král, Petr, Hong, Seungpyo
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.02.2022; John Wiley and Sons Inc; Wiley
• Subjects: Amino acids; binding avidity; Breast Neoplasms - metabolism; Cell Adhesion; Cell Line, Tumor; Dendrimers - metabolism; dendrimer–peptide conjugate; Engineering; hierarchically multivalent architectures; Humans; Ligands; Molecular weight; multivalent binding; Nanoparticles; Nanoparticles - metabolism; peptide engineering; Peptides; Peptides - metabolism; Physical Phenomena; Polyethylene Glycols - metabolism; Proteins; Retention; Shear stress; Signal transduction; T cell receptors; hierarchically multivalent architectures; multivalent binding; binding avidity; dendrimer-peptide conjugate; peptide engineering
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202103098

The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity‐based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer–peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC‐based HMAs. This study presents a novel surface platform that utilizes hierarchically controlled multivalent binding of peptides. Using dendrimers, peptides, and linkers as building blocks, the role of each component and the effect of surface presentation/arrangement of different peptides on surface binding are investigated. The results presented herein provide guidelines for the effective use of biomolecular multivalent interactions for various biomedical applications.