Studies of the Interactions of Nanoparticles with Lipid Bilayers - PDF document

Studies of the Interactions of Nanoparticles with Lipid Bilayers Using a Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) Samuel R. Howell Institut Laue-Langevin, EPN Campus, 71 Avenue des Martyrs, Grenoble CEDEX 9 - France Abstract Studies of lipid bilayers, and the effect of gold nanoparticles on them, were undertaken using a quartz-crystal microbalance with dissipation monitoring (QCM-D). These measurements aimed to determine whether DOPC and DOPC & cholesterol lipid bilayers had been formed on a quartz (SiO 2 ) surface after injection and incubation. This was followed by injection of gold nanoparticles, and subsequent observation of their effect on the QCM-D output. A qualitative discussion on the effect of nanoparticles on the stability and properties of these bilayers follows based on our findings. In addition, the success of different vesicle preparation methods is discussed, with the aim of better informing future work using these bilayers. Key words: Lipid, QCM-D, Bilayer, Surface, Vesicle 1 Introduction The words ’lipid bilayer’ do not encapsulate the impor- tance of what they describe. At the beginning of this four week research project, the author of this report was, for lack of a better word, ignorant, as to the profound importance of lipid bilayers - and hence too the inher- Fig. 1. The structure of the DOPC phospholipid used in the ent value in studying them. One need not look far to study (Source: Abel et al.) [3] see the importance of lipid bilayers - they are essential structures in biology, forming the framework of life’s fun- damental building block - the living cell [1] . The bound- foreseen effects occurred, for example in the widespread ary of cells is important to numerous processes includ- use of thalidomide as an antiemetic for morning sick- ness [10] . The devastating effect of not fully understand- ing the transport of species to and from a cell’s interior, biological mechanisms involving the body’s immune re- ing thalidomide’s pharmacological properties stands as sponse and the effectiveness and toxicity of different drug an example of the importance of understanding the tox- molecules [2] . These boundaries are not just studied for icology of new medicinal treatments. The same must be scientific interest; it is crucial we understand lipid bilay- done for these nanoparticle-based cancer therapies and ers to advance our knowledge of human biology, medicine all future medical technologies, and as such we must ex- and the next generation of disease treatment. plore the interaction of nanoparticles with what they Such was the motivation of this study - to gain in- would encounter in the body. In short - as lipid bilayers sight into a particular interaction which may have sig- constitute the boundary of living cells, it is important nificant medical importance - the interaction of gold to explore how nanoparticles behave with them. In our nanoparticles with a lipid bilayer [4] . For now it will suf- case, this was done using a quartz crystal microbalance fice to say that gold nanoparticles have potential uses - a machine first developed by William H. King Jr. at Esso Engineering labs in the 60s [11] . In efforts to advance in cancer therapies due to their unique optical proper- ties (namely in theranostics ) [5–9] . If these properties are the ease of studying bilayers, we also consider the test- to be fully utilised, however, one must assess the effect ing of different techniques used in making their vesicle precursor as a focus of the research [12,13] . In particular, of introducing them into the body. Drug development has had catastrophic consequences in the past when un- for the bilayer formed of the phospholipid 1,2-dioleoyl- 21 October 2017

Fig. 3. The space-filling structure of the phospholipid DPPC (Source: Nelson, Biological Physics) [21] . Fig. 2. The structure of cholesterol (Source: Atkins Physical Chemistry) [14] . sn-glycero-3-phosphocholine , which shall here on be re- ferred to by it’s acronym, DOPC. Bilayer production in- volves several steps: first making a solution of lipid at the desired concentration, filtering vesicles by size and perhaps incorporating other molecules into the result- ing vesicle structures as well. The only bilayers studied here were those consisting of pure DOPC (See Figure ) and a DOPC & cholesterol mix (Figure 2). The motive of this, as well as more fruitful detail of our studies, are expanded in the next section. 2 Theory 2.1 Phospholipids Fig. 4. Diagram showing the structure of a generic phospho- lipid bilayer (Source: Nelson, Biological Physics) [21] . Lipids are given the following definition in biochemistry: bilayer , and consists of two layers of lipids, as the name suggests. These layers are oriented such that the tails “ any of a large group of organic compounds that are of the lipids are contained in the interior of the layer, esters of fatty acids (simple lipids, such as fats and with the hydrophilic heads forming the outer boundary waxes) or closely related substances (compound lipids, in contact with the solvent. There is minimal solvent such as phospholipids): usually insoluble in water but contained within the boundary interior, where the tails soluble in alcohol and other organic solvents [15] ” reside. A diagram of a lipid bilayer is shown in Figure 4. One must remember when looking at these diagrams A perfectly apt definition, for those familiar with chem- however that the structure is not rigid - the phospho- istry. A more general description of lipids would be lipid molecules will be in a state of complex, random that they are molecules consisting of two parts - a hy- thermal agitation at any time. drophilic, water-hating tail segment, and a hydrophilic, So why exactly do these bilayers form? The reason is water-loving head group. This general amphiphilic [16] rooted in thermodynamics - and the argument behind structure is made clearer in Figure 3, which shows the it is particularly strong for dual-tailed phospholipids space-filling model of the phospholipid DPPC. Phos- such as DOPC, although it also applies to single tailed pholipids, such as DPPC, are an abundant form of molecules. Essentially, when water molecules come into – ) in the head group. lipid, with a phosphate (PO 4 contact with the hydrophobic tail(s) of a lipid, they as- These phospholipids, first discovered in 1847 by French sume an ordered structure around the tail to minimise chemist Theodore Nicolas Gobley [17] , are extremely im- the number of water molecules interacting with the tail. portant in biology, as the bilayer structure they adopt This is an attempt to minimise the interaction energy forms the boundary of living cells [18–20] . between the tail and water, and is known as the hy- drophobic effect - the ’cage’ the water molecules form around the tails is known as a solvation cage [2] . How- 2.2 Lipid Bilayers ever, from an energetic and entropic point of view, this is quite thermodynamically costly - the water molecules Lipids can form different structures, with the exact in this solvation cage form less hydrogen bonds than shape and size depending on various properties - such their bulk counterparts, and are thus in a compara- as the concentration and shape of the lipid monomer tively high energy state. They are also less disordered units [1] . The structure of interest to us is called the lipid than molecules in the bulk, so a loss of entropy is as- 2