AbstractNanoparticles are increasingly found in modern technologies, ranging from biosensors to food additives. However, how the size, shape and surface chemistry of nanoparticles affect their cytotoxic effects is not well understood. Cytotoxicity tests using dye-based assays give limited information on the fundamental interactions between NPs and cell membranes that lead to cellular entry and resulting toxicity. It is also difficult to examine such interactions in vitro and thus using membrane models represents a promising complementary approach.
This project explores how the physicochemical properties of polyamidoamine (PAMAM) dendrimers (as model nanoparticles; 2.5 nm or 4.5 nm in size, with either NH2 or hydrophobic C12 terminal groups) influence their interactions with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) membrane models (bilayers, multilayers, and mesophases), probed with techniques including atomic force microscopy and synchrotron X-ray scattering.
We found that adding PAMAM dendrimers to DOPC bilayers caused an increase in the bilayer thickness, an effect that depended on the dendrimer size and concentration. The presence of the dendrimers induced significant structural disruptions to DOPC multilayers, evident from the reduced coherence length and the enlarged paracrystalline disorder in the multilayers.
Using high pressure small angle X-ray scattering (HP-SAXS), we also studied the effect of the dendrimers on the transitions between different POPE mesophases. The lamellar (Lα and Lβ) phases bear structural resemblance to cell membranes, whilst the highly curved inverse hexagonal (HII) phase is considered an analogue for membrane fusion intermediates, which would form during nanoparticle cellular uptake. We observed the suppression of the HII phase in the presence of high concentrations of 4.5 nm dendrimers and the stabilisation of a highly swollen fluid lamellar phase. These structural changes in the model membranes caused by the nano-sized dendrimers give us unprecedented physical insight into the energetic processes of nanoparticle cellular uptake and the fundamentals of nanotoxicity.
|Date of Award||23 Jan 2020|
|Supervisor||Wuge H Briscoe (Supervisor) & Robert M Richardson (Supervisor)|