Graphene Oxide Nanosheets Retard Cellular Migration via Disruption of Actin Cytoskeleton

Abstract

Graphene and graphene-based nanomaterials are broadly used for various biomedical applications due to their unique physiochemical properties. However, how graphene-based nanomaterials interact with biological systems has not been thoroughly studied. This study shows that graphene oxide (GO) nanosheets retard A549 lung carcinoma cell migration through nanosheet-mediated disruption of intracellular actin filaments. After GO nanosheets treatment, A549 cells display slower migration and the structure of the intracellular actin filaments is dramatically changed. It is found that GO nanosheets are capable of absorbing large amount of actin and changing the secondary structures of actin monomers. Large-scale all-atom molecular dynamics simulations further reveal the interactions between GO nanosheets and actin filaments at molecular details. GO nanosheets can insert into the interstrand gap of actin tetramer (helical repeating unit of actin filament) and cause the separation of the tetramer which eventually leads to the disruption of actin filaments. These findings offer a novel mechanism of GO nanosheet induced biophysical responses and provide more insights into their potential for biomedical applications.

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

“…Acute or chronic inflammation responses are interfering with the normal physiological functions of important organs [42,43]. C-BNM are known to induce either physical or biological damage to the cell membrane, membranes of organelles along with destabilization of actin filaments, the cytoskeleton and effecting the cell cycle [44][45][46]. At the tissue and cellular levels, the mechanisms responsible for inflammation are based on disruption of various barriers (e.g., alveolar-capillary barrier, blood-brain barrier), infiltration of immune cells and their interaction with molecules released from injured cells (disease associated molecular patterns) or with nanoparticles themselves [47].…”

Interfacing Graphene-Based Materials With Neural Cells

“…Common mechanisms of cytotoxicity of G nanosheets have been reported in literature on different cell types, and include the physical interaction with cell membranes (Seabra et al, 2014 ); disruption of cell cytoskeleton (Tian et al, 2017 ); oxidative stress due to production of reactive oxygen species (ROS; Chen M. et al, 2016 ; Mittal et al, 2016 ); mitochondrial damage (Pelin et al, 2017 ); DNA damage, such as chromosomal fragmentation, DNA strand breakages, point mutations and oxidative DNA alterations (Akhavan et al, 2012 ; Fahmi et al, 2017 ); autophagy (Chen et al, 2014 ); and apoptosis and/or necrosis (Lim et al, 2016 ). Furthermore, published data suggest that GO is less toxic than G, rGO and hydrogenated-G; smaller nanosheets are less toxic than large flakes and highly dispersible G solutions are safer than aggregating ones (Donaldson et al, 2006 ; Akhavan et al, 2012 ; Bianco, 2013 ; Kurapati et al, 2016 ; Ou et al, 2016 ).…”

NanoEHS beyond toxicity – focusing on biocorona

“…Due to computational limitations, most of the computational studies in literature aimed to uncover high-resolution structural and dynamic information have been focused on simulations of single proteins interacting with a single NP, which is usually not the case in vitro and in vivo . Recently, computational modelling efforts have been devoted to understand the effects of NPs on complex biological processes involving multiple biomolecules, such as protein-protein recognition 231, 232 and protein aggregation. 215, 227, 233, 234 In the following section, we will focus on recent computational and modelling studies concerning the effects of NPs on protein aggregation, where efficient modelling of multiple proteins in the presence of NPs in silico becomes necessary.…”