Now showing 1 - 7 of 7
  • Publication
    Bionano Interactions: A Key to Mechanistic Understanding of Nanoparticle Toxicity
    The new paradigm in the assessment of toxicity of nanomaterials relies on a mechanistic understanding of the organism’s response to an exposure to foreign materials from the initial, molecular level interactions to signaling and regulatory cascades. Here, we present a methodology to quantify the essential interactions at the bionano interface, which can be used in combination with the adverse outcome pathway analysis to build mechanism-based predictive schemes for toxicity assessments. We introduce a set of new, advanced descriptors of the nanomaterials, which refer to their ability to bind biomolecules and trigger the pathways via the molecular initiating events.
  • Publication
    Using single nanoparticle tracking obtained by nanophotonic force microscopy to simultaneously characterize nanoparticle size distribution and nanoparticle-surface interactions
    Comprehensive characterization of nanomaterials for medical applications is a challenging and complex task due to the multitude of parameters which need to be taken into consideration in a broad range of conditions. Routine methods such as dynamic light scattering or nanoparticle tracking analysis provide some insight into the physicochemical properties of particle dispersions. For nanomedicine applications the information they supply can be of limited use. For this reason, there is a need for new methodologies and instruments that can provide additional data on nanoparticle properties such as their interactions with surfaces. Nanophotonic force microscopy has been shown as a viable method for measuring the force between surfaces and individual particles in the nano-size range. Here we outline a further application of this technique to measure the size of single particles and based on these measurement build the distribution of a sample. We demonstrate its efficacy by comparing the size distribution obtained with nanophotonic force microscopy to established instruments, such as dynamic light scattering and differential centrifugal sedimentation. Our results were in good agreement to those observed with all other instruments. Furthermore, we demonstrate that the methodology developed in this work can be used to study complex particle mixtures and the surface alteration of materials. For all cases studied, we were able to obtain both the size and the interaction potential of the particles with a surface in a single measurement.
      349Scopus© Citations 8
  • Publication
    In depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation
    Advances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core-shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes.
      253Scopus© Citations 14
  • Publication
    Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury
    Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.
      424Scopus© Citations 5
  • Publication
    Classification and biological identity of complex nano shapes
    Everywhere in our surroundings we increasingly come in contact with nanostructures that have distinctive complex shape features on a scale comparable to the particle itself. Such shape ensembles can be made by modern nano-synthetic methods and many industrial processes. With the ever growing universe of nanoscale shapes, names such as “nanoflowers” and “nanostars” no longer precisely describe or characterise the distinct nature of the particles. Here we capture and digitise particle shape information on the relevant size scale and create a condensed representation in which the essential shape features can be captured, recognized and correlated. We find the natural emergence of intrinsic shape groups as well-defined ensemble distributions and show how these may be analyzed and interpreted to reveal novel aspects of our nanoscale shape environment. We show how these ideas may be applied to the interaction between the nanoscale-shape and the living universe and provide a conceptual framework for the study of nanoscale shape biological recognition and identity.
      289Scopus© Citations 34
  • Publication
    Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles
    Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily due to the absence of a microscopic picture of the surface presentation of the polymer. Here a detailed NMR analysis reveals three types of dynamic ethylene glycol units on PEG-grafted SiO2 nanoparticles (NPs) of the type commonly evaluated as long-circulating theranostic nano-probes; a narrow fraction with fast dynamics associated with the chain ends; a broadened fraction spectrally overlapped with the former arising from those parts of the chain experiencing some dynamic restriction; and a fraction too broad to be observed in the spectrum arising from units closer to the surface/graft which undergo slow motion on the NMR timescale. We demonstrate that ethylene glycol units transition between fractions as a function of temperature, core size, PEG chain length and surface coverage and demonstrate how this distribution affects colloidal stability and protein uptake. The implications of the findings for biological application of grafted nanoparticles are discussed in the context of accepted models for surface ligand conformation. This journal is
      16Scopus© Citations 8
  • Publication
    Coarse-grained model of adsorption of blood plasma proteins onto nanoparticles
    (AIP Publishing, 2015-12) ;
    We present a coarse-grained model for evaluation of interactions of globular proteins with nanoparticles (NPs). The protein molecules are represented by one bead per aminoacid and the nanoparticle by a homogeneous sphere that interacts with the aminoacids via a central force that depends on the nanoparticle size. The proposed methodology is used to predict the adsorption energies for six common human blood plasma proteins on hydrophobic charged or neutral nanoparticles of different sizes as well as the preferred orientation of the molecules upon adsorption. Our approach allows one to rank the proteins by their binding affinity to the nanoparticle, which can be used for predicting the composition of the NP-protein corona. The predicted ranking is in good agreement with known experimental data for proteinadsorption on surfaces.
      539Scopus© Citations 61