Abstract
The zeta potential of the protein corona around carboxyl particles has been measured using tunable resistive pulse sensing (TRPS). A simple and rapid assay for characterising zeta potentials within buffer, serum and plasma is presented monitoring the change, magnitude and distribution of proteins on the particle surface. First, we measure the change in zeta potential of carboxyl-functionalised nanoparticles in solutions that contain biologically relevant concentrations of individual proteins, typically constituted in plasma and serum, and observe a significant difference in distributions and zeta values between room temperature and 37 °C assays. The effect is protein dependent, and the largest difference between the two temperatures is recorded for the γ-globulin protein where the mean zeta potential changes from −16.7 to −9.0 mV for 25 and 37 °C, respectively. This method is further applied to monitor particles placed into serum and/or plasma. A temperature-dependent change is again observed with serum showing a 4.9 mV difference in zeta potential between samples incubated at 25 and 37 °C; this shift was larger than that observed for samples in plasma (0.4 mV). Finally, we monitor the kinetics of the corona reorientation for particles initially placed into serum and then adding 5 % (V/V) plasma. The technology presented offers an interesting insight into protein corona structure and kinetics of formation measured in biologically relevant solutions, i.e. high protein, high salt levels, and its particle-by-particle analysis gives a measure of the distribution of particle zeta potential that may offer a better understanding of the behaviour of nanoparticles in solution. Graphical The relative velocity of a nanoparticle as it traverses a nanopore can be used to determine its zeta potential. Monitoring the changes in translocation speeds can therefore be used to follow changes to the surface chemistry/composition of 210 nm particles that were placed into protein rich solutions, serum and plasma. The particle-by-particle measurements allow the zeta potential and distribution of the particles to be characterised, illustrating the effects of protein concentration and temperature on the protein corona. When placed into a solution containing a mixture of proteins, the affinity of the protein to the particle’s surface determines the corona structure, and is not dependent on the protein concentration Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-016-9678-6) contains supplementary material, which is available to authorized users.
Highlights
In recent years, synthesis methods for nanoparticles have evolved to the extent that particle size, shape and composition can be modified [1,2,3,4] and this had led in turn to great advances in the field of diagnostics [5, 6], drug delivery [7,8,9] and technology platforms [10, 11]
We describe a recent adaptation to inorganic pores that uses a tunable elastomeric pore termed tunable resistive pulse sensing (TRPS) [14, 24,25,26,27,28,29,30,31,32,33,34,35,36]; the pore can be stretched in real time to suit the sample
It is important to note each blockade depicted in the signal trace is indicative of a single particle as it passes through the pore, highlighting the advantages of using particle-by-particle technologies such as TRPS
Summary
Synthesis methods for nanoparticles have evolved to the extent that particle size, shape and composition can be modified [1,2,3,4] and this had led in turn to great advances in the field of diagnostics [5, 6], drug delivery [7,8,9] and technology platforms [10, 11]. Ensemble techniques that take measurements on several particles simultaneously and provide an average measurement can underestimate subpopulations within multimodal samples [12, 13], and a raft of technologies have appeared to help tackle this [14, 15] Such technologies offer an ability to quantify the population of particles with single particle resolution building an understanding that not all particles are created equal and there exists distributions such as particle size or ligand density. One such technology is based on the Coulter Counter principle, referred to as resistive pulse sensing (RPS) [16,17,18]. TRPS is becoming an increasingly common variation of RPS for the characterisation of biological and inorganic nanomaterials [24, 36] and since its conception has been tested against alternative technologies such as DLS/
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