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.
|Publication status||Published - 2022 Feb 2|
Bibliographical noteFunding Information:
W.J. and J.B. contributed equally to this work. This study was partially supported by the National Science Foundation (NSF) under grant # DMR‐1808251. The authors also acknowledge the partial support from the Wisconsin Head & Neck Cancer SPORE Grant (P50‐DE026787), the Falk Medical Research Trust ‐ Catalyst Awards Program, and the National Research Foundation of Korea (NRF) under grant # 2021R1A4A3024237.
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Chemical Engineering(all)
- Materials Science(all)
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Physics and Astronomy(all)