Role of Curvature-Sensing Proteins in the Uptake of Nanoparticles with Different Mechanical Properties

Daphne Montizaan, Catherine Saunders, Keni Yang, Sajitha Sasidharan, Sourav Maity, Catharina Reker-Smit, Marc C.A. Stuart, Costanza Montis, Debora Berti, Wouter H. Roos, Anna Salvati*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Nanoparticles of different properties, such as size, charge, and rigidity, are used for drug delivery. Upon interaction with the cell membrane, because of their curvature, nanoparticles can bend the lipid bilayer. Recent results show that cellular proteins capable of sensing membrane curvature are involved in nanoparticle uptake; however, no information is yet available on whether nanoparticle mechanical properties also affect their activity. Here liposomes and liposome-coated silica are used as a model system to compare uptake and cell behavior of two nanoparticles of similar size and charge, but different mechanical properties. High-sensitivity flow cytometry, cryo-TEM, and fluorescence correlation spectroscopy confirm lipid deposition on the silica. Atomic force microscopy is used to quantify the deformation of individual nanoparticles at increasing imaging forces, confirming that the two nanoparticles display distinct mechanical properties. Uptake studies in HeLa and A549 cells indicate that liposome uptake is higher than for the liposome-coated silica. RNA interference studies to silence their expression show that different curvature-sensing proteins are involved in the uptake of both nanoparticles in both cell types. These results confirm that curvature-sensing proteins have a role in nanoparticle uptake, which is not restricted to harder nanoparticles, but includes softer nanomaterials commonly used for nanomedicine applications.

Original languageEnglish
Article number2303267
Number of pages13
JournalSmall
Volume19
Issue number39
Early online date26-May-2023
DOIs
Publication statusPublished - 27-Sept-2023

Keywords

  • curvature-sensing proteins
  • liposome-coated silica
  • membrane curvature generation
  • nanoparticle rigidity
  • nanoparticle uptake

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