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.
Highlights
Gaining precise control over the cellular entry pathway of nanomaterials is key in achieving cytosolic delivery, accessing subcellular environments, and regulating toxicity
Successful cytosolic delivery is a prerequisite for effective probing of the intracellular environment, modulation of gene expression, and cell-based therapies[2]
By probing the interactions in this three-dimensional parameter space, we identified four types of translocation of nanoparticles across model cell membranes, featuring distinct cellular entry pathways
Summary
Gaining precise control over the cellular entry pathway of nanomaterials is key in achieving cytosolic delivery, accessing subcellular environments, and regulating toxicity This precise control requires a fundamental understanding of the behavior of nanomaterials at the bio-nano interface. There is a compelling need to fundamentally understand the interactions at the nanomaterial-cell membrane interface to decipher the cellular entry pathways of nanomedicines which determines their intracellular trafficking cascade and cellular fate. A systems-level understanding of the interactions that elucidates the collective effect of multiple key physicochemical parameters at the bio-nano interface is urgently needed. To achieve such understanding, techniques and tools that allow quantitative analysis of these parameters need to be developed[1]. We discuss the distinct intracellular trafficking routes and cellular fates following the observed entry pathways, and the utilization of these subcellular routes in varying cellular applications
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
