Dynamics of receptor-mediated nanoparticle internalization into endothelial cells

Area of Science:

• Biomedical Engineering
• Computational Biology
• Nanomedicine

Background:

• Nanoparticles show potential for targeted drug delivery, particularly to inflamed endothelial cells in atherosclerosis.
• Understanding nanoparticle-cell interactions is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To develop a computational model of nanoparticle internalization into endothelial cells.
• To investigate the factors influencing nanoparticle uptake, including receptor-ligand binding and cell mechanics.
• To inform the design of nanoparticles for treating atherosclerosis.

Main Methods:

• Developed a computational model simulating nanoparticle internalization driven by receptor-ligand binding.
• Incorporated cell membrane and cytoplasm deformation as limiting factors.
• Analyzed internalization kinetics, binding dynamics, and stress distribution.

Main Results:

• Predicted an optimal nanoparticle size for maximal internalization speed, aligning with experimental data.
• Identified the significant roles of bond characteristics, local cell mechanics, and external forces.
• Quantified the interplay between nanoparticle properties and cellular responses.

Conclusions:

• The computational model provides insights into nanoparticle internalization mechanisms.
• Findings support the optimization of nanoparticle design for enhanced drug delivery in atherosclerosis treatment.
• The model can guide future development of targeted nanomedicines.