CCP5 Flagship project - CG mapping tools

Study of interactions between polymer nanoparticles and cell membranes at atomistic levels


1Scientific Computing Department, Science and Technology Facilities Council, Daresbury Laboratory, Sci-Tech Daresbury, Warrington WA4 4AD, UK
2Manchester Pharmacy School, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, the University of Manchester, UK

This is an important research work [1] relates to the emerging field of nanotoxicology. The work was carried out in response to the invited talk for the Royal Society Discussion � Cell Adhesion Century: culture breakthrough, on 28-29 April 2014. The work demonstrated the use of DL_FIELD to setup the complex models, DL_POLY to run the simulations and DL_ANALYSER to produce the results.

As nanoparticles are produced at industrial scales, it is important to investigate their toxicological effects upon human health and the environment. In addition, degradation of bulk materials in the environment, such as polymeric packaging materials, can occur to generate micro fragments or even individual polymer chains. Indeed, it is known that nanoparticles can easily be ingested and adsorbed into living organisms and yet studies regarding their biocompatibility and cytotoxicity effects are still quite limited. Whilst extra-cellular effects of nanoparticles are significant, their adhesion and entry into cells bring greater potential of both desired and toxic effects. This can take place by endocytosis, direct diffusion or membrane disruption. Clearly, there is a pressing need to understand how nanoparticles interact and adhere to cell membranes and the underlying factors and mechanisms by which nanoparticles are transferred into cells. Such knowledge would be important in the design of nanoparticles with surface morphologies that do not bring deleterious effects to living organisms, while still achieving their intended functions.

A series of molecular simulations has been carried out, to investigate polymer nanoparticles� interaction with the cell membranes, namely, the interactions of polyethylene (PE) and polystyrene (PS) nanoparticles with the POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid cell membrane. These polymers are produced in a huge quantity annually and are found in abundance in industry, as well as the environment. The simulations are based on fully atomistic models using DL_POLY_4 package and DL_FIELD was used to set up the force field models. The aim is to investigate the initial stages of the polymer adsorption behaviour and their underlying mechanistic details, rather than exploring the whole process of subsequent particle uptake by the membranes.

Figures below illustrate the adsorption of PE particle into the membrane.

It is found that irreversible adhesion can be initiated by insertion of dangling chain ends from the polymer into the hydrophobic interior of the POPC membrane. In addition, the side groups, as well as the nature of chain entanglements, can also influence the behaviour of the membrane interaction and subsequent uptake of the nanoparticles. For instance, the initial polymer insertion can be facilitated by the reorientation of the PE nanoparticles such that the chain segments are approximately aligned with those of hydrocarbon chain segments from the POPC membrane. As the polymers were immersed in the membrane, dissolutions can take place, depending on the chain topology and the extent of entanglement. Left figure above shows the initial irreversible insertion of a PE chain end (highlight as a blue sphere) into the membrane. This is followed by reorientation of the polymer particle before embedded into the membrane, right figure above.

Figure below shows a snapshot of the adsorption of PS onto the membrane, initiated by an anchoring chain end (highlight as a blue sphere).

[1] C. W. Yong, Phil. Trans. R. Soc. B370: 20140036.


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