Substrate stiffness regulates cellular uptake of nanoparticles

Changjin Huang, Peter J. Butler, Sheng Tong, Hari S. Muddana, Gang Bao, Sulin Zhang

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


Nanoparticle (NP)-bioconjugates hold great promise for more sensitive disease diagnosis and more effective anticancer drug delivery compared with existing approaches. A critical aspect in both applications is cellular internalization of NPs, which is influenced by NP properties and cell surface mechanics. Despite considerable progress in optimization of the NP-bioconjugates for improved targeting, the role of substrate stiffness on cellular uptake has not been investigated. Using polyacrylamide (PA) hydrogels as model substrates with tunable stiffness, we quantified the relationship between substrate stiffness and cellular uptake of fluorescent NPs by bovine aortic endothelial cells (BAECs). We found that a stiffer substrate results in a higher total cellular uptake on a per cell basis, but a lower uptake per unit membrane area. To obtain a mechanistic understanding of the cellular uptake behavior, we developed a thermodynamic model that predicts that membrane spreading area and cell membrane tension are two key factors controlling cellular uptake of NPs, both of which are modulated by substrate stiffness. Our experimental and modeling results not only open up new avenues for engineering NP-based cancer cell targets for more effective in vivo delivery but also contribute an example of how the physical environment dictates cellular behavior and function.

Original languageEnglish
Pages (from-to)1611-1615
Number of pages5
JournalNano Letters
Issue number4
StatePublished - Apr 10 2013


  • Substrate stiffness
  • cancer therapy
  • cellular spreading
  • cellular uptake
  • membrane tension
  • nanoparticles

ASJC Scopus subject areas

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


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