Understanding the synergistic effect of physicochemical properties of nanoparticles and their cellular entry pathways
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s42003-020-0917-1.pdf
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Published version
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4.87 MB
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Author(s) • • • • •
Lin, Jiaqi
Miao, Lei
Zhong, Grace
Lin, Chih-Hsin
Dargazangy, Roozbeh
Alexander-Katz, Alfredo
Date Issued
2020
Journal
Communications Biology
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2020, The Author(s). Gaining precise control over the cellular entry pathway of nanomaterials is key in achieving cytosolic delivery, accessing subcellular environments, and regulating toxicity. However, this precise control requires a fundamental understanding of the behavior of nanomaterials at the bio-nano interface. Herein, we report a computational study investigating the synergistic effect of several key physicochemical properties of nanomaterials on their cellular entry pathways. By examining interactions between monolayer-protected nanoparticles and model cell membranes in a three-dimensional parameter space of size, surface charge/pKa, and ligand chemistry, we observed four different types of nanoparticle translocation for cellular entry which are: outer wrapping, free translocation, inner attach, and embedment. Nanoparticle size, surface charge/pKa, and ligand chemistry each play a unique role in determining the outcome of translocation. Specifically, membrane local curvature induced by nanoparticles upon contact is critical for initiating the translocation process. A generalized paradigm is proposed to describe the fundamental mechanisms underlying the bio-nano interface.
MIT Department
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s42003-020-0917-1