Nanomanipulation of Ligand Nanogeometry Modulates Integrin/Clathrin-Mediated Adhesion and Endocytosis of Stem Cells

Bohan Yin, Qin Zhang, Jiaxiang Yan, Yingying Huang, Chuanqi Li, Jiareng Chen, Chunyi Wen, Siu Hong Dexter Wong, Mo Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

Nanosubstrate engineering can be a biomechanical approach for modulating stem cell differentiation in tissue engineering. However, the study of the effect of clathrin-mediated processes on manipulating this behavior is unexplored. Herein, we develop integrin-binding nanosubstrates with confined nanogeometries that regulate clathrin-mediated adhesion- or endocytosis-active signaling pathways for modulating stem fates. Isotropically presenting ligands on the nanoscale enhances the expression of clathrin in cells, thereby facilitating uptake of dexamethasone-loaded nanoparticles (NPs) to boost osteogenesis of stem cells. In contrast, anisotropic ligand nanogeometry suppresses this clathrin-mediated NP entry by strengthening the association between clathrin and adhesion spots to reinforce mechanotransduced signaling, which can be abrogated by the pharmacological inhibition of clathrin. Meanwhile, inhibiting focal adhesion formation hinders cell spreading and enables a higher endocytosis efficiency. Our findings reveal the crucial roles of clathrin in both endocytosis and mechanotransduction of stem cells and provide the parameter of ligand nanogeometry for the rational design of biomaterials for tissue engineering.

Original languageEnglish
Pages (from-to)9160-9169
Number of pages10
JournalNano Letters
Volume23
Issue number19
DOIs
Publication statusPublished - 26 Jul 2023

Keywords

  • cell−substrate interaction
  • endocytosis
  • ligand nanogeometry
  • Nanosubstrate engineering
  • stem cell differentiation

ASJC Scopus subject areas

  • Bioengineering
  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanical Engineering

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