Key Role of Choline Head Groups in Large Unilamellar Phospholipid Vesicles for the Interaction with and Rupture by Silica Nanoparticles

Abstract

For highly abundant silica nanomaterials, detrimental effects on proteins and phospholipids are postulated as critical molecular initiating events that involve hydrogen‐bonding, hydrophobic, and/or hydrophilic interactions. Here, large unilamellar vesicles with various well‐defined phospholipid compositions are used as biomimetic models to recapitulate membranolysis, a process known to be induced by silica nanoparticles in human cells. Differential analysis of the dominant phospholipids determined in membranes of alveolar lung epithelial cells demonstrates that the quaternary ammonium head groups of phosphatidylcholine and sphingomyelin play a critical and dose‐dependent role in vesicle binding and rupture by amorphous colloidal silica nanoparticles. Surface modification by either protein adsorption or by covalent coupling of carboxyl groups suppresses the disintegration of these lipid vesicles, as well as membranolysis in human A549 lung epithelial cells by the silica nanoparticles. Furthermore, molecular modeling suggests a preferential affinity of silanol groups for choline head groups, which is also modulated by the pH value. Biomimetic lipid vesicles can thus be used to better understand specific phospholipid–nanoparticle interactions at the molecular level to support the rational design of safe advanced materials.

Reaction with Water Vapor Defines Surface Reconstruction and Membranolytic Activity of Quartz Milled in Different Molecular Environments

“…In fact, no correlation between ROS generation and membranolytic activity was often observed [ 3b,10a,36 ] but a large panel of silica and silica‐based materials confirmed the central role of NFS in the establishment of specific interactions with zwitterionic phospholipids in cell membranes. [ 10b,37 ] To measure this interaction, we used non‐internalizing cells (red blood cells, RBC) that limit the potential interaction with particles to the outer lipid bilayer of their cytoplasmatic membrane. RBC does not have a role in the inflammatory or fibrotic responses induced by quartz particles, but their membrane is a convenient model [ 38 ] and the hemolysis test is largely used to evaluate the pro‐inflammatory activity of quartz dust.…”

Physico-Chemical Approaches to Investigate Surface Hydroxyls as Determinants of Molecular Initiating Events in Oxide Particle Toxicity

“…Lysosomal membrane perturbation leads to the activation of the inflammasome machinery that triggers the maturation and release of pro-inflammatory interleukins, including interleukin IL-1β and IL-18 (Figure 12B) [97,98]. Silica cytotoxicity and haemolysis correlated well with the available external surface area of the particles [99,100], suggesting that, for SiO 2 , the particle surface rules the interaction with biomembrane.…”

“…Several particle physico-chemical parameters, including size, shape, agglomeration/aggregation state, and differences in surface chemistry (e.g., surface hydrophilicity/hydrophobicity and charge), have been reported to influence the interaction with model membranes [122]. Several studies demonstrated that crystalline and amorphous SiO 2 (nano)particles may destabilize zwitterionic vesicles of phosphatidylcholine (PC) lipids in different size ranges [26,100,[123][124][125][126]. The same effects have been observed for colloidal and pyrogenic nanosilica interacting with mixed vesicles which mimic the PL composition of lung cells [100].…”

“…Several studies demonstrated that crystalline and amorphous SiO 2 (nano)particles may destabilize zwitterionic vesicles of phosphatidylcholine (PC) lipids in different size ranges [26,100,[123][124][125][126]. The same effects have been observed for colloidal and pyrogenic nanosilica interacting with mixed vesicles which mimic the PL composition of lung cells [100]. Silica nanoparticles ranging from 50 to 500 nm induced dose-dependent dye leakage from 1,2-dioleoyl-snglycero-3-phosphocholine (DOPC) liposomes [126], which is indicative of compromised membrane integrity, with similar efficiency when compared by surface area dose [100].…”

Continuous-time binding kinetics of graphene oxide quantum dots and lipid bilayers dominated by hydrogen bonding: effect of nanoparticles' protein corona and membrane components

“…Because synthetic small unilamellar vesicles (SUVs) and supported lipid bilayers (SLBs) make the structural and chemical control of model membranes much simpler, they are often used as model systems of cell membranes to study fundamental biophysical processes. 12,13 Many recent studies have reported interactions between GOFNs and SLBs. Li et al suggested that the attachment of GO to membranes was promoted by hydrogen bonding by using SLBs.…”