Physiochemical Effects of Nanoparticles on Cell Nuclear Complex Pore Transport: A Coarse-Grained Computational Model

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cell Biology

Background:

• Controlling nanoparticle-cell nucleus interactions is vital for biomedical applications like gene delivery and tumor therapy.
• Existing research highlights the influence of nanoparticle size, shape, and ligand density on cellular uptake, but nuclear entry mechanisms remain under-investigated.

Purpose of the Study:

• To computationally evaluate how nanoparticle size, shape, and karyopherin ligand grafting density affect transport through the nuclear pore complex.
• To provide a framework for designing nanoparticles for precise nucleus-targeted therapy.

Main Methods:

• Development of a computational framework to simulate nanoparticle transport through the nuclear pore complex.
• Parametric evaluation of nanoparticle physical properties (size, shape, ligand density) and their impact on nuclear uptake.

Main Results:

• Smaller spherical nanoparticles face lower energy barriers for nuclear entry compared to larger ones.
• High grafting density of ligands significantly alters nanoparticle dynamics during active transport.
• Nanoparticle shape and morphology are critical determinants of nuclear uptake pathways.

Conclusions:

• Nanoparticle nuclear uptake is governed by a complex interplay between particle physicochemical properties and nuclear characteristics.
• This work offers a systematic understanding of nuclear uptake for nanoparticles, viruses, and bacteria.
• A controllable design strategy for manipulating nanoparticle-nucleus interactions is established, with implications for medicine, bioimaging, and biosensing.