Material implants trigger host reactions generated by cells, such as macrophages, which display dynamic adhesion and polarization including M1 inflammatory state and M2 anti-inflammatory state. Creating materials that enable diverse nanoscale display of integrin-binding groups, such as RGD ligand, can unravel nanoscale recruitment and ligation of integrin, which modulate cellular adhesion and activation. Here, we synthesized gold nanorods (GNRs) with various nanoscale anisotropies (i.e., aspect ratios, ARs), but in similar surface areas, and controlled their substrate conjugation to display an anisotropic ligand nanogeometry without modulating ligand density. Using nanoscale immunolabeling, we demonstrated that highly anisotropic ligand-coated GNRs ("AR4" and "AR7") facilitated the recruitment of integrin β1 on macrophages to their nanoscale surfaces. Consequently, highly anisotropic GNRs (e.g., "AR4" and "AR7") elevated the adhesion and M2 state of macrophages, with the inhibition of their M1 state in the culture and mice, entailing rho-associated protein kinase. This nanoscale anisotropic nanogeometry provides a novel and critical parameter to be considered in the generation of biomaterials to potentially modulate host reactions to the implants for immunomodulatory tissue regeneration.
Bibliographical noteFunding Information:
Project 31570979 is supported by the National Natural Science Foundation of China. This work is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project no. 14220716); the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (reference no.: 04152836); the Chow Yuk Ho Technology Centre for Innovative Medicine, and The Chinese University of Hong Kong. The work was partially supported by Hong Kong Research Grants Council Theme-based Research Scheme (ref. T13-402/17-N). The work was partially supported by grants from Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. 14120118, 14160917, 9054014 N_CityU102/15, T13-402/17-N); National Natural Science Foundation of China (81772404, 81430049, and 81772322); and Hong Kong Innovation Technology Commission Funds (ITS/UIM-305). This study was also supported in part by SMART program, Lui Che Woo Institute of Innovative Medicine.
© Copyright 2019 American Chemical Society.
Copyright 2019 Elsevier B.V., All rights reserved.
- anisotropic nanogeometry
- integrin recruitment
- macrophage adhesion
- macrophage polarization
- nanoscale immunolabeling
ASJC Scopus subject areas
- Materials Science(all)
- Condensed Matter Physics
- Mechanical Engineering