Differential modulation of endothelial cytoplasmic protrusions after exposure to graphene-family nanomaterials

Herdeline Ann M. Ardoña, John F. Zimmerman, Kevin Shani, Su Hwan Kim, Feyisayo Eweje, Dimitrios Bitounis, Dorsa Parviz, Evan Casalino, Michael Strano, Philip Demokritou, Kevin Kit Parker

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Engineered nanomaterials offer the benefit of having systematically tunable physicochemical characteristics (e.g., size, dimensionality, and surface chemistry) that highly dictate the biological activity of a material. Among the most promising engineered nanomaterials to date are graphene-family nanomaterials (GFNs), which are 2-D nanomaterials (2DNMs) with unique electrical and mechanical properties. Beyond engineering new nanomaterial properties, employing safety-by-design through considering the consequences of cell-material interactions is essential for exploring their applicability in the biomedical realm. In this study, we asked the effect of GFNs on the endothelial barrier function and cellular architecture of vascular endothelial cells. Using micropatterned cell pairs as a reductionist in vitro model of the endothelium, the progression of cytoskeletal reorganization as a function of GFN surface chemistry and time was quantitatively monitored. Here, we show that the surface oxidation of GFNs (graphene, reduced graphene oxide, partially reduced graphene oxide, and graphene oxide) differentially affect the endothelial barrier at multiple scales; from the biochemical pathways that influence the development of cellular protrusions to endothelial barrier integrity. More oxidized GFNs induce higher endothelial permeability and the increased formation of cytoplasmic protrusions such as filopodia. We found that these changes in cytoskeletal organization, along with barrier function, can be potentiated by the effect of GFNs on the Rho/Rho-associated kinase (ROCK) pathway. Specifically, GFNs with higher surface oxidation elicit stronger ROCK2 inhibitory behavior as compared to pristine graphene sheets. Overall, findings from these studies offer a new perspective towards systematically controlling the surface-dependent effects of GFNs on cytoskeletal organization via ROCK2 inhibition, providing insight for implementing safety-by-design principles in GFN manufacturing towards their targeted biomedical applications.

Original languageEnglish (US)
Article number100401
StatePublished - Apr 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Materials Science (miscellaneous)
  • Safety, Risk, Reliability and Quality
  • Safety Research
  • Public Health, Environmental and Occupational Health


  • 2-D nanomaterials
  • Cell-material interactions
  • Cytoplasmic protrusions
  • Endothelial cells
  • Nanosafety


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