Mechanochemical Cellular Membrane Internalization of Nanohydrogels: A Large-Scale Mesoscopic Simulation

Area of Science:

• Biophysics
• Materials Science
• Cell Biology

Background:

• Nanohydrogels are promising for drug delivery and tissue engineering.
• Understanding their cellular internalization pathways is crucial for optimizing applications.

Purpose of the Study:

• To investigate the mechanochemical cellular internalization pathways of homogeneous and heterogeneous nanohydrogels.
• To elucidate the role of nanohydrogel properties (crosslink density, encapsulation) in membrane interaction.

Main Methods:

• Large-scale dissipative particle dynamics simulations.
• Steered molecular dynamics simulations.

Main Results:

• Membrane internalization is dictated by nanohydrogel crosslink density and encapsulation ability.
• Homogeneous nanohydrogels with high crosslink density and low encapsulation are partially wrapped.
• Homogeneous nanohydrogels with low crosslink density and high encapsulation permeate the membrane.
• Local lipid nanodomains form at the membrane-nanohydrogel interface due to differential diffusion.
• Yolk@shell heterogeneous nanohydrogels exhibit reduced contact area and lipid nanodomains, mitigating cellular toxicity.

Conclusions:

• Nanohydrogel properties critically determine cellular internalization mechanisms.
• Heterogeneous nanohydrogels offer a strategy to minimize membrane disruption and potential toxicity.
• Findings guide the design of nanohydrogels for advanced biomedical applications.