Small, Clickable, and Monovalent Magnetofluorescent Nanoparticles Enable Mechanogenetic Regulation of Receptors in a Crowded Live-Cell Microenvironment

• Published in: Nano letters 2019-06, Vol.19 (6), p.3761-3769
• Main Authors: Kwak, Minsuk, Gu, Wonji, Jeong, Heekyung, Lee, Hyunjung, Lee, Jung-uk, An, Minji, Kim, Yong Ho, Lee, Jae-Hyun, Cheon, Jinwoo, Jun, Young-wook
• Format: Article
• Language: English
• Subjects: Actins - analysis; Adherens Junctions - ultrastructure; Cadherins - analysis; Cell Line, Tumor; Cellular Microenvironment; Click Chemistry; Fluorescent Dyes - chemistry; Humans; Magnetite Nanoparticles - chemistry; Micromanipulation; Nanoparticles - chemistry; Optical Imaging; Polyethylene Glycols - chemistry
• ISSN: 1530-6984; 1530-6992; 1530-6992
• DOI: 10.1021/acs.nanolett.9b00891

Multifunctional magnetic nanoparticles have shown great promise as next-generation imaging and perturbation probes for deciphering molecular and cellular processes. As a consequence of multicomponent integration into a single nanosystem, pre-existing nanoprobes are typically large and show limited access to biological targets present in a crowded microenvironment. Here, we apply organic-phase surface PEGylation, click chemistry, and charge-based valency discrimination principles to develop compact, modular, and monovalent magnetofluorescent nanoparticles (MFNs). We show that MFNs exhibit highly efficient labeling to target receptors present in cells with a dense and thick glycocalyx layer. We use these MFNs to interrogate the E-cadherin-mediated adherens junction formation and F-actin polymerization in a three-dimensional space, demonstrating the utility as modular and versatile mechanogenetic probes in the most demanding single-cell perturbation applications.