Nanoparticle interactions with live cells: Quantitative fluorescence microscopy of nanoparticle size effects

Area of Science:

• Biomedical Engineering
• Cell Biology
• Nanotechnology

Background:

• Engineered nanomaterials enter human cells via endocytosis.
• Understanding nanoparticle-cell interactions is crucial for nanomedicine.
• Nanoparticle size significantly influences cellular uptake and endocytic pathways.

Purpose of the Study:

• To systematically analyze the cellular uptake of fluorescent nanoparticles (NPs) across a size range of 3.3-100 nm.
• To elucidate the distinct endocytic mechanisms governed by NP size.
• To investigate the role of NP size in triggering cellular internalization.

Main Methods:

• Utilized live-cell spinning disk confocal microscopy.
• Employed quantitative image analysis to track NP-cell interactions.
• Studied time courses of NP association with the cell membrane and subsequent internalization.

Main Results:

• NPs <10 nm accumulated at the plasma membrane before internalization.
• NPs of 100 nm were directly internalized without prior membrane accumulation.
• Surface charge did not affect the internalization mechanism for larger NPs.

Conclusions:

• Nanoparticle size is a critical determinant of endocytic mechanism.
• Distinct size-dependent interactions with the endocytic machinery govern NP uptake.
• Understanding these size-dependent mechanisms is key for predicting nanoparticle behavior in biological systems.