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Understanding the synergistic effect of physicochemical properties of nanoparticles and their cellular entry pathways.

ABSTRACT: 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.

SUBMITTER: Lin J

PROVIDER: S-EPMC7192949 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Understanding the synergistic effect of physicochemical properties of nanoparticles and their cellular entry pathways.

Lin Jiaqi J Miao Lei L Zhong Grace G Lin Chih-Hsin CH Dargazangy Roozbeh R Alexander-Katz Alfredo A

Communications biology 20200430 1

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 bet ...[more]

PMID: 32355216

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Project description:The unique properties of single walled carbon nanotubes (SWCNTs) make them viable candidates for versatile implementation in the next generation of biomedical devices for targeted delivery of chemotherapeutic agents or cellular-sensing probes. Such implementation requires user-tailored changes in SWCNT's physicochemical characteristics to allow for efficient cellular integration while maintaining nanotubes' functionality. However, isolated reports showed that user-tailoring could induce deleterious effects in exposed cells, from decrease in cellular proliferation, to changes in cellular adhesion, generation of reactive oxygen species or phenotypical variations, just to name a few. Before full implementation of SWCNTs is achieved, their toxicological profiles need to be mechanistically correlated with their physicochemical properties to determine how the induced cellular fate is related to the exposure conditions or samples' characteristics. Our study provides a comprehensive analysis of the synergistic cyto- and genotoxic effects resulted from short-term exposure of human lung epithelial cells to pristine (as manufactured) and user-tailored SWCNTs, as a function of their physicochemical properties. Specifically, through a systematic approach we are correlating the nanotube uptake and nanotube-induced cellular changes to the sample's physicochemical characteristics (e.g., metal impurities, length, agglomerate size, surface area, dispersion, and surface functionalization). By identifying changes in active hallmarks involved in cell-cell connections and maintaining epithelial layer integrity, we also determine the role that short-term exposure to SWCNTs plays in the overall cellular fate and cellular transformation. Lastly, we assess cellular structure-function relationships to identify non-apoptotic pathways induced by SWCNTs exposure that could however lead to changes in cellular behavior and cellular transformation. Our results show that the degree of cell transformation is a function of the physicochemical properties of the SWCNT, with the nanotube with higher length, higher metal content and larger agglomerate size reducing cell viability to a larger extent. Such changes in cell viability are also complemented by changes in cell structure, cycle and cell-cell interactions, all responsible for maintaining cell fate.

Dataset Information

Understanding the synergistic effect of physicochemical properties of nanoparticles and their cellular entry pathways.

Publications

Understanding the synergistic effect of physicochemical properties of nanoparticles and their cellular entry pathways.

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