Protein corona mitigates the cytotoxicity of graphene oxide by reducing its physical interaction with cell membrane

Abstract

Many recent studies have shown that the way nanoparticles interact with cells and biological molecules can vary greatly in the serum-containing or serum-free culture medium. However, the underlying molecular mechanisms of how the so-called "protein corona" formed in serum medium affects nanoparticles' biological responses are still largely unresolved. Thus, it is critical to understand how absorbed proteins on the surfaces of nanoparticles alter their biological effects. In this work, we have demonstrated with both experimental and theoretical approaches that protein BSA coating can mitigate the cytotoxicity of graphene oxide (GO) by reducing its cell membrane penetration. Our cell viability and cellular uptake experiments showed that protein corona decreased cellular uptake of GO, thus significantly mitigating the potential cytotoxicity of GO. The electron microscopy images also confirmed that protein corona reduced the cellular morphological damage by limiting GO penetration into the cell membrane. Further molecular dynamics (MD) simulations validated the experimental results and revealed that the adsorbed BSA in effect weakened the interaction between the phospholipids and graphene surface due to a reduction of the available surface area plus an unfavorable steric effect, thus significantly reducing the graphene penetration and lipid bilayer damaging. These findings provide new insights into the underlying molecular mechanism of this important graphene protein corona interaction with cell membranes, and should have implications in future development of graphene-based biomedical applications.

Membrane destruction-mediated antibacterial activity of tungsten disulfide (WS2)

“…In our current study, WS 2 nanosheets were probably partially coated with protein FBS in the cell viability assays, even though the culture media of A549 and HEP G2 cells were replaced with WS 2 -loaded serum-free media aer reaching $80% conuence. 57,58 In other words, our current A549 and HEP G2 cell experiments are more similar to Chae and coworkers' experiment on HEK293f as mentioned above. On the contrary, in the antibacterial experiments, the WS 2 nanosheets were kept "naked" during the entire incubation with bacteria.…”

“…While a well-documented mechanism is still absent, a possible reason is proposed to be the existence of nuclear membrane in eukaryotic cells. In addition, as suggested from our previous studies, 57 biomolecules like proteins can rapidly adsorb onto nanomaterial surfaces to form protein corona which can effectively reduce their cytotoxicity. In our current study, WS 2 nanosheets were probably partially coated with protein FBS in the cell viability assays, even though the culture media of A549 and HEP G2 cells were replaced with WS 2 -loaded serum-free media aer reaching $80% conuence.…”

Differential cytotoxic effects of graphene and graphene oxide on skin keratinocytes

“…All together, these observations lead to conclude that, also compared to other carbon nanomaterials, GOs and especially FLG exert very weak cytotoxicity on skin keratinocytes. Even though GBMs cytotoxicity could be reduced by a protein corona due to the presence of serum inside culture medium6768, the present results suggest an acceptable biocompatibility of these materials, both after short acute exposure times (i.e. 24 h) and after long-term exposure to low GBMs concentrations (0.1 μg/mL, up to 10 days).…”

Biological interactions of carbon-based nanomaterials: From coronation to degradation

“…Similarly, Chong et al [84] also found that adsorption of serum proteins onto GO drastically reduced their cytotoxicity towards A549 lung carcinoma cells and found that GO exhibits a dramatic enhancement of adsorption capacity compared to SWCNTs. In a subsequent study, coating of GO with BSA was suggested to reduce cytotoxicity towards A549 cells by reducing the physical interaction of GO with the cell membrane [85]. It is noted, however, that A549 is a notoriously robust carcinoma cell line not reflective of normal cell physiology.…”