Colloids and Surfaces B: Biointerfaces 108 (2013) 120–126 Contents lists available at SciVerse ScienceDirect Colloids and Surfaces B: Biointerfaces jou rn al hom epage: www.elsevier.com/locate/colsurfb Probing the interaction of oppositely charged gold nanoparticles with DPPG and DPPC Langmuir monolayers as cell membrane models Adriano A. Torrano a,1 , Ângela S. Pereira a , Osvaldo N. Oliveira Jr. b,∗ , Ana Barros-Timmons a a Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal b São Carlos Institute of Physics, USP, CP 369, 13560-970 São Carlos, SP, Brazil a r t i c l e i n f o Article history: Received 30 August 2012 Received in revised form 8 February 2013 Accepted 11 February 2013 Available online 5 March 2013 Keywords: Cell membrane models Langmuir monolayers Nano-bio interface Gold nanoparticles Phospholipids a b s t r a c t The growing use of nanoparticles in a variety of applications calls for detailed studies of their toxicology, which in turn require understanding the interactions between nanoparticles and living cells. Since simu- lating the interaction with real cell membranes is rather complex, Langmuir monolayers (LMs) have been used to mimic the first barrier encountered by a nanoparticle as it approaches a biological membrane to assess molecular-level interactions. In this study, we show how oppositely charged gold nanoparti- cles (Au-NPs) interact with monolayers of the zwitterionic dipalmitoylphosphatidyl choline (DPPC) and negatively charged dipalmitoylphosphatidyl glycerol (DPPG). The monolayers were spread on subphases containing two concentrations of either negatively charged Au-NPs coated with citrate anions or pos- itively charged Au-NPs functionalized with the cationic polyelectrolyte poly(allylamine hydrochloride) (PAH). For DPPG, electrostatic effects dominated which depended strongly on the NPs capping agent, being obviously larger for the positive nanoparticles. The in-plane elasticity for DPPG monolayers within the surface pressure range corresponding to real cell membranes increased with adsorption of positively charged NPs, but decreased with the negative ones. For the zwitterionic DPPC, on the other hand, sig- nificant effects only occurred for negatively charged NPs, including a decrease in elasticity. Therefore, it is concluded that the nature, namely the charge of the capping agents, is crucial for the interaction of charged NPs with the cell membrane. © 2013 Elsevier B.V. All rights reserved. Colloidal gold nanoparticles have been applied since ancient times due to their peculiar optical properties, but recently the opportunity arose for their use in biological applications. Although gold nanoparticles (Au-NPs) are comprised of an inert material, biocompatibility remains a key issue. The safe use of synthetic nanoparticles (NPs) in living systems requires evaluation of their possible toxicity, which depends on the dynamic forces at the interface between the nanoparticles and the cell membranes, the so-called nano-bio interface. At present, it is not possible to describe all the interactions taking place in this region. In a review on this issue Nel et al. [1] analyzed the interactions from the perspec- tive of forces governing colloidal chemistry, and found that the effects depend mainly on the material properties, on the coating of the nanoparticles and on the changes in their surface properties induced by the suspending medium. The complexity of this relation is increased by the cell heterogeneity over the membrane surface ∗ Corresponding author at: Instituto de Física de São Carlos, USP, CP 369, 13566- 590 São Carlos, SP, Brazil. Tel.: +55 1633739825; fax: +55 1633715365. E-mail address: chu@ifsc.usp.br (O.N. Oliveira Jr.). 1 Current address: Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), Butenandtstrasse 5-13 (E), 81377 Munich, Germany. on the order of 10–200 nm [1–3], and therefore the interaction will depend on the precise site of interaction of the nanoparticle at the cell’s surface. The most numerous molecules forming the cell mem- brane are lipids, such as cholesterol and phospholipids; they are responsible for the structural integrity of the membrane, which can be considered as two parallel monolayers with their polar groups on the outside surface (inner and outer surfaces) and the non-polar tails pointing inward. From this arrangement, one can infer that hydrophobicity is used as an effective barrier by living cells. Within the lipid bilayer the membrane contains a variety of proteins and polysaccharides which, together with the head groups of the phos- pholipids, make the membrane very sensitive to surface charges [4,5]. Hence, the nano-bio interface may be affected even by minute changes in its components properties. In fact, two nanoparticles made up of the same material, but produced via different synthetic routes, may present distinct interactions with a given cell [1]. On the other hand, different cell lines may react in distinct ways toward the very same NPs. Consequently, any findings about the nanotox- icity of a particular material are, in principle, only valid under very specific production and experimental conditions [1,6,7]. The biocompatibility of more than 130 types of NPs intended for therapeutic use, including gold colloids, polymers, metal oxides, quantum dots and fullerenes, was assessed in vivo and in vitro 0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfb.2013.02.014