Endothelial Cell Selectivity to Nanoparticles Depends on Mechanical Phenotype

Pouria Fattahi, Yin Ting Yeh, Tiankai Zhao, Mousa Younesi, Changjin Huang, Mauricio Terrones, Siyang Zheng, Justin L. Brown, Dan Dongeun Huh, Sulin Zhang, Peter J. Butler

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Endothelial cells (ECs) elongate in the direction of blood flow, are stiffer, and are considered atheroprotective in areas of the vasculature where flow-induced shear stress is high and unidirectional and are softer, atherogenic, and polygonal in areas experiencing oscillatory multidirectional flow. To understand the precise roles of EC mechanics and morphology in the uptake of therapeutic nanoparticles (NPs) by atherogenic endothelium, human aortic ECs are induced to adopt prescribed shapes and areas imposed by microcontact patterned adhesive islands. NP uptake per cell increases with increasing spreading area and decreases with increasing cell aspect ratio at constant cell spreading area. Biomechanical analysis shows that elongated cells exhibit higher cellular stress and stiffer membranes than cells with low aspect ratios, indicating a strong correlation between morphology, mechanical phenotype, and NP uptake. Further, ECs elongated by high laminar shear endocytosed NPs to a far lesser extent than those that are nonelongated in the chaotic, lower shear areas when cocultured in the same chamber. Results indicate that conditions leading to atherogenesis, such as low, chaotic shear-induction of EC polygonal morphology may be used to increase the uptake of therapeutic NPs as a preventative measure against atherosclerosis.

Original languageEnglish (US)
Article number2300137
JournalAdvanced Materials Interfaces
Volume10
Issue number18
DOIs
StatePublished - Jun 27 2023

All Science Journal Classification (ASJC) codes

  • Mechanics of Materials
  • Mechanical Engineering

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