Why synthetic virus-like nanoparticles can achieve higher cellular uptake efficiency?

Area of Science:

• Biophysics
• Nanotechnology
• Cellular Biology

Background:

• Nanoparticle cellular uptake can be enhanced by mimicking viral spiky surfaces.
• The precise effect of surface topological structure on nanoparticle translocation across cell membranes remains unclear.

Purpose of the Study:

• To investigate how the surface topological structure of virus-like nanoparticles (VLPs) influences their interaction with and penetration of lipid bilayers.
• To elucidate the mechanisms by which VLP spikes facilitate cellular uptake.

Main Methods:

• Dissipative particle dynamics simulations were employed to model the interactions between VLPs and lipid bilayers.
• Analysis focused on critical force for penetration and the VLP internalization pathway.
• Comparisons were made between VLPs and spherical nanoparticles.

Main Results:

• VLPs with longer, sparser spikes exhibited superior penetrability.
• VLP spikes were observed to perturb the lipid bilayer structure upon adhesion.
• Spikes increased lateral bilayer defects, reduced vertical deformation, and lowered local lipid density during translocation, collectively enhancing penetrability compared to spherical nanoparticles.

Conclusions:

• The surface topological structure, specifically spike length and density, significantly impacts nanoparticle translocation across cell membranes.
• VLPs demonstrate enhanced cellular uptake capabilities due to spike-mediated modulation of lipid bilayer properties.
• Findings provide insights into cellular uptake mechanisms and support the development of VLPs for biomedical applications.