Nanowire Based Mechanostimulating Platform for Tunable Activation of Natural Killer Cells

Viraj Bhingardive, Avishay Edri, Anna Kossover, Guillaume Le Saux, Bishnu Khand, Olga Radinsky, Muhammed Iraqi, Angel Porgador, Mark Schvartzman

Research output: Contribution to journalArticlepeer-review

Abstract

The understanding of the activation mechanism of natural killer (NK) cells has been traditionally based on the biochemical interaction of NK cell receptors with the ligands presenting on target cells. Yet, how physical features of the NK cell environment, such as stiffness and nanoscale topography, regulate the activity of NK cells, is unknown. An artificial microenvironment is developed for NK cell stimulation based on variably elongated nanowires functionalized with activating antigens and used it as a tunable model system to study the separate and cumulative effects of elasticity and nanotopography on NK cell activation. It is found that late signaling, degranulation, and cytokine production in NK cells consistently vary with nanowire length, and it is maximized for the longest nanowires, measuring ≈20 µm in length. Intriguingly, a similar trend is observed for nanowires lacking antigens, albeit with a lower activation magnitude overall, indicating that chemical and mechanical stimuli independently determine the activation of NK cells. The demonstrated tuning of the activation of NK cells by nanoscale physical features of their environment not only provides an important insight into the regulation mechanism of these lymphocytes, but also paves the way to rationally designed nanomaterials for controlled ex vivo activation of NK cells in immunotherapy.

Original languageEnglish
Article number2103063
JournalAdvanced Functional Materials
Volume31
Issue number26
DOIs
StatePublished - 1 Jun 2021

Keywords

  • NK cells
  • activation
  • biofunctionalization
  • mechanosensing
  • nanowires

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