Assessment of the Biological Effects of Nanomaterials Symposium

Europe/Stockholm
F3 (KTH - Royal Institute of Technology)

F3

KTH - Royal Institute of Technology

Lindstedtsväg 26
Emppu Salonen (Helsinki University of Technology)
Description

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Overview

Nanomaterials are nowadays part of our everyday life. They are used in cosmetics products. We breathe nanoparticles on a daily basis since they are produced by the present-day automobile engines. Meanwhile, nanomaterials are also being developed for biomedical purposes, thus sooner or later they are likely used as carriers of drugs, improving our health.

How much do we actually know about the environmental and health effects of nanomaterials? Too little. Is there possibly reason for concern? Yes. Is it possible that nanomaterials could be used for applications improving the quality our lives, if we just understood their properties well enough. Definitely yes.

The bottom line is that the environmental and health effects of nanomaterials are of global concern, both in view of assessing the impact of nanomaterials discharged into nature and for a safe and transparent development of nanotechnology, especially in relation to novel applications in biomedicine. At present, nanomaterials are already produced at an industrial scale and the number of consumer products featuring nanomaterials is increasing at a rapid pace. At the same time, detailed understanding of the potential biological and ecological effects of nanomaterials and the related legislation are clearly lagging behind. Some of the key questions related to these issues are the transport, uptake and transformation of nanomaterials in air, soil and natural waters, as well as within biological organisms.

To treat these questions and related issues, the Symposium on "Assessment of Biological Effects of Nanomaterials" will be organized by Nordita on the campus of KTH (The Royal Institute of Technology, Stockholm, Sweden). The Symposium is a full, two-day scientific meeting with invited presentations, contributed talks as well as discussion sessions related to important and topical questions around the themes of nanomaterials acting on biological systems.

One of the main overall objectives of the Symposium is to promote synergy in this field through discussions and collaborations, matching theoretical and experimental groups, coupling the theoretical work as closely as possible with experiments.

We are expecting participants from different fields of science, such as physics, chemistry, biochemistry, biology, environmental sciences, and medical sciences. The Symposium is free of charge and open for anyone to attend. However, we kindly ask for all of the participants to register in advance to the Symposium, so that we have a clear idea of the number of participants.

In order to apply for a presentation in the Symposium, please send an abstract of your presentation, either in DOC or PDF format (max 1 page) to the program chairman Emppu Salonen (e-mail: Firstname.Lastname@tkk.fi). Deadline: January 15, 2009.

The topics of the Symposium include (but are not limited to):

  • Theory and simulations applied to nanomaterials acting on biological systems
  • Coupling theory and simulations with experiments as closely as possible
  • Environmental fate of nanomaterials
  • Bioavailability and toxicology
  • Fundamental interactions of nanomaterials with biological systems
  • Green nanotechnology
  • Biomedical applications, drug delivery
  • Characterization, detection, and monitoring
  • Exposure and risk assessment, regulation policies

Symposium speakers (confirmed)

  • Baoshan Xing, University of Massachusetts, USA
  • Pekka Koskinen, University of Jyväskylä, Finland
  • Jayne Wallace, University of Oxford, UK
  • Luca Monticelli, INSERM, France / Helsinki University of Technology, Finland
  • Sijie Lin, Clemson University, USA
  • Anna Shvedova, West Virginia University, USA
  • Yuri Volkov, Trinity College Dublin, Ireland
  • Peter Tieleman, University of Calgary, Canada
  • Olle Edholm, KTH, Sweden
  • Peter Wick, EMPA, Switzerland
  • Anne Thoustrup Saber, National Institute of Occupational Health, Denmark

    • 9:30 AM 10:00 AM
      Coffee and tea 30m
    • 10:00 AM 10:15 AM
      Symposium opening 15m
      Speaker: Dr Emppu Salonen (Helsinki University of Technology)
    • 10:15 AM 11:00 AM
      Carbon nanotubes: a hazard free opportunity? 45m
      Nanoparticulate materials and among them, carbon nanotubes (CNTs) are a new type of materials that generate high expectations due to their unique physical, chemical and optical properties. Due to the predictably increasing production of various types of carbon nanotubes and other nanoparticle-containing products, it can be expected that environmental and public exposure to engineered nanoparticles will also increase in parallel. If and in how far CNTs are able to affect human health is currently quite controversially discussed. Here we summarize how CNTs are produced and processed in order to identify critical parameters, which have to be included in the toxicological assessment. A special effort was made to balance the adverse and benefit effects of CNTs on cell physiology. Among toxicological effects, we report about CNTs in medical applications and we discuss two selected examples of prospective applications of CNTs in nano-medicine, which have realistic chances to achieve ready-to-market products in a few years.
      Speaker: Dr Peter Wick (EMPA, Swiss Laboratories for Materials Testing and Research, Switzerland)
    • 11:00 AM 11:45 AM
      Molecular dynamics simulations of the interactions of carbon nanotubes with biomolecules 45m
      There is great interest in exploiting the novel properties of carbon nanotubes (CNTs) for use in biology and medicine. For example, CNTs have potential application in drug delivery, cancer and gene therapy, and as components of biosensors. However, prior to their usage we need to both develop methods to overcome the hydrophobicity-induced aggregation of CNTs, and also to understand the fundamental interactions of CNTs with cellular components. Dissolution of CNTs has been facilitated by the noncovalent adsorption of both lipids and detergents onto the surface of CNTs. We investigate the interaction of both lipids and detergents with single-walled CNTs via coarse-grained molecular dynamics [1,2]. We present evidence that the mechanism of adsorption of these amphiphiles onto a CNT is dependent upon amphiphile concentration. Furthermore, the chirality of the CNT influences the amphiphile wrapping angle for low amphiphile concentration. Recently, designed synthetic peptides have also proven effective at dispersing CNTs. This approach has the significant advantage that the nature of the peptides coating the CNTs can be controlled by specifying the amino acid sequence. Hence, peptides can be designed such that the peptide/CNT complex may target specific tissue. One such designed synthetic peptide, nano-1 [3], folds into an amphiphilic α-helix in the presence of CNTs and leads to CNT dispersion. We implement molecular dynamics to investigate the self-assembly of nano-1 onto CNTs, using both a coarse-grained and atomistic approach. Using this multi-scaled method, we show that nano-1 interacts with CNTs in a preferential orientation. Furthermore, the charged surfaces of nano-1 facilitate inter-peptide interactions within the peptide/CNT complex, promoting helix stability. We have also performed coarse-grained molecular dynamics simulations of CNTs penetrating through lipid bilayers [4]. This work is motivated by the use of CNTs as nanoinjectors. We show that CNTs extract lipids from the bilayer upon penetration. These lipids interact with both the inner and outer CNT surface, with lipids in the CNT interior potentially “blocking” the tube. [1] Wallace, E. J.; Sansom, M. S. P. Nano Lett. 2007, 7, 1923-1928. [2] Wallace, E. J.; Sansom, M. S. P. Nanotechnology 2009, 20, 045101. [3] Dieckmann, G. R.; Dalton, A. B.; Johnson, P. A.; Razal, J.; Chen, J.; Giordano, G. M.; Munoz, E.; Musselman, I. H.; Baughman, R. H.; Draper, R. K. J. Am. Chem. Soc. 2003, 125, 1770-1777. [4] Wallace, E. J.; Sansom, M. S. P. Nano Lett. 2008, 8, 2751-2756.
      Speaker: Dr Jayne Wallace (University of Oxford, UK)
    • 11:45 AM 1:15 PM
      Lunch 1h 30m
    • 1:15 PM 2:00 PM
      Inflammatory and genotoxic effects of nanoparticles -Focus on nanoparticles used in the paint and lacquer industry 45m
      Different kinds of particles have been shown to induce genotoxic damage after deposition in the lung. This may result in cancer if the DNA damage is not repaired or if selective apoptosis of the damaged cells fails. A primary mechanism of particle-induced genotoxicity has been attributed to the surface characteristics. A decade ago a secondary pathway for genotoxicity was proposed on the basis of the finding that carbon black exposed rats developed tumours similar to DEP exposed rats, despite the fact that carbon black is almost devoid of PAH´s on the surface. The fact that tumour formation in rats has been found to be paralleled by the degree of chronic neutrophilic inflammation led to the idea about a relationship between particle-induced inflammation and genotoxicity. Likewise, most human cancers are accompanied by the infiltration of inflammatory cells and a wide range of chronic inflammatory diseases predispose to cancer in the affected organ. The genotoxic effect of particle-induced inflammation is related to the release of reactive oxygen species by the inflammatory process. It has been demonstrated that the inflammatory response depends on the particle size. Exposure studies have shown that ultrafine particles cause more inflammation in the lungs of rodents than exposure to the same mass concentration of fine particles. The greater surface area has been suggested to be responsible for the greater inflammatory response of the ultrafine particles. This is based on a linear correlation between surface area of relatively inert particles and inflammatory response measured by the total number of neutrophils in rats. Thus, the genotoxic effects of PM can either be directly due to surface properties of the particles or due to ROS released by the inflammatory process. I will discuss inflammatory and genotoxic effects of nanoparticles on the background of results obtained in an ongoing project, Nanokem. The aims of NanoKem are to identify and characterize the essential risks caused by exposure to nanoparticles in the paint- and lacquer industry.
      Speaker: Dr Anne Thoustrup Saber (National Research Centre for the Working Environment, Copenhagen, Denmark)
    • 2:00 PM 2:30 PM
      Coffee & tea 30m
    • 2:30 PM 3:15 PM
      Toxicity of carbon nanotubes to the lung: from mechanisms to regulatory consequence 45m
      Advancements in nanotechnology and broad applications of nanomaterials raise the issue of their potential adverse health effects particularly in occupational and environmental settings. Among different nanomaterials, Single-Walled Carbon Nanotubes (SWCNT) – with their unique physico-chemical, electronic and mechanical properties – are emerging as important objects of toxicological studies. However, toxic effects of SWCNT have not been well characterized, especially with respect to pulmonary outcomes. We will present data demonstrating that SWCNT in doses relevant to potential occupational exposures may exert their toxic effects in the lung of exposed animals in vivo. We documented an unusual and robust inflammatory and fibrogenic response closely associated with the progression of oxidative stress in the lungs. Because realistic exposures to SWCNT are likely to occur in conjunction with other pathogenic influences, e.g., microbial infections, our finding of compromised bacterial clearance in the lungs of SWCNT-exposed mice are of great practical importance. This talk will address important issues of respiratory toxicity of aspired vs inhaled SWCNT in relation to their ability to cause pulmonary injury. Finally, the mechanisms of toxicity will be discussed in the context of current regulations of protection and their sufficiency in occupational settings. Acknowledgements: supported by NIOSH OH008282, NORA 92700Y, 7th Framework EU: FP7-NMP-2007.
      Speaker: Dr Anna Shvedova (West Virginia University, USA)
    • 3:15 PM 4:00 PM
      Imaging at nanoscale can be deceiving 45m
      Nanoscale imaging techniques can be accurate, but sometimes things are not as they seem. I will present two cases where the imaging technique itself causes the measured phenomenon. First case relates to TEM imaging of a metal atom diffusing in graphene, and the second relates to STM imaging of small potassium islands on graphite. In both cases theory is needed to interpret the experimental findings.
      Speaker: Dr Pekka Koskinen (University of Jyväskylä, Finland)
    • 4:00 PM 4:45 PM
      Discussion 45m
      Speaker: Dr Emppu Salonen (Helsinki University of Technology)
    • 4:45 PM 6:30 PM
      Break 1h 45m
    • 6:30 PM 9:30 PM
      Symposium dinner 3h

      Venue TBA

    • 9:15 AM 10:00 AM
      High Content Imaging and Analysis approach to investigation of nanoparticle/cell interactions 45m
      Rapid development of nanotechnology consistently increases the likelihood of human contact with environmentally presented and manufactured nanomaterials, i.e. the tiny objects ranging in size from one to several hundreds of nanometres and featuring an extreme diversity in shapes and physico-chemical properties. However, there is still very little definitive systematic information about the consequences of interactions of nano-scale objects with human cells of diverse origin and therefore safety-related issues are high on the agenda in the emerging scientific area of nanomedicine. On the other hand, optimistic expectations are associated with the opportunities of using the nanoparticles as a new class of drug delivery systems, arising from the fact that the finite, but tunable size of the engineered nanostructures used as drug delivery vehicles can impose very precise nano-scale drug distribution barriers at the level of cells, tissues and entire organism thereby eliminating undesirable side effects pertinent to most contemporary medicines. High content imaging and analysis (HCA) approach provides a unique integrated technological toolkit for visualization and physical characterization of nanoparticle-cell interactions. An exceptional aspect of this approach is that it is possible to identify individual cell, as well as population responses associated with nanoparticle exposure, as in this way subtle effects on small groups of cells within the whole, which could be averaged out by only screening the whole set, are fully registered and elucidated. We provide here an overview of HCA application scenarios for screening the safety and intracellular distribution of nanomaterials with promising biomedical application potential. Supported by the Health Research Board of Ireland, Science Foundation of Ireland SRC BioNanoInteract and EU FP-6 Consortium NanoInteract.
      Speaker: Prof. Yuri Volkov (Trinity College Dublin, Ireland)
    • 10:00 AM 10:45 AM
      Interaction of fullerene with model membranes: Computer simulation studies 45m
      Carbon nanoparticles are biologically active and can enter easily different kinds of cells. It is not clear how these materials enter cell membranes and what are the mechanisms of cell damage. Recently it has been found that natural organic matter (NOM) interacts strongly with fullerene and carbon nanotubes, altering their interaction with cells. Gallic acid is one of the main components of NOM. The mixture of fullerene and gallic acid can cause cell membrane damage and cell death by unknown mechanisms [1]. Our goal is to investigate the molecular interactions between fullerene and model membranes, in the absence and in the presence of NOM, and to explore different possible mechanisms of cell damage, using computer simulations. We have developed a coarse-grained (CG) model for simple carbon nanoparticles (fullerenes and nanotubes) compatible with the MARTINI CG force field for lipids and proteins [2-4]. Our CG model reproduces reasonably well partitioning of fullerene between different organic solvents. We use both unbiased and non-equilibrium MD techniques to characterize the thermodynamics and the mechanism of permeation of fullerene clusters through DOPC lipid bilayers. We show that high fullerene concentrations induce changes in the structural and elastic properties of the lipid bilayer, but these are not large enough to cause a direct mechanical damage to the membrane [5]. In order to study the combined effect of fullerene and gallic acid on membranes properties, we use molecular dynamics simulations with an atomistic representation. Our results suggest that gallic acid significantly changes the distribution of fullerene and its interaction with cell membranes. We hypothesize that changes in the membrane elastic properties could alter membrane protein functioning and therefore cause cell damage. [1] E Salonen et al., Small, 4 (2008) 1986. [2] SJ Marrink et al., J Phys Chem B, 108 (2004) 750. [3] SJ Marrink et al., J Phys Chem B, 111 (2007) 7812. [4] L Monticelli et al., J Chem Theory Comput, 4 (2008) 819. [5] J Wong-ekkabut et al., Nature Nanotech, 3 (2008), 363.
      Speaker: Dr Luca Monticelli (INSERM Paris, France)
    • 10:45 AM 11:15 AM
      Coffee & tea 30m
    • 11:15 AM 12:00 PM
      Partitioning between water and lipid bilayers 45m
      The thermodynamics of interactions between the lipid bilayer and other molecules determines to a large extend the transport rate of these molecules across the bilayer as well as the nature of the process involved in partitioning. In the past few years we have studied these interactions for a range of organic molecules, for lipids, cholesterol, fullerenes, and models of carbon nanotubes. The large gradients in density, order, and hydrophobicity in a bilayer make partitioning a highly non-trivial process that is difficult to predict. Insertion of polar or charged molecules in particular involves significant changes in the bilayer structure, which dominate the cost of partitioning. An extreme example of this is the partitioning of multiple arginine side chains into the bilayer, which is a highly non-additive process with most of the energetic cost determined by the formation of an initial water defect. Similar observations are made for transport of lipids. Coarse-grained simulations of fullerene show little membrane perturbation, but investigations of nanotubes show significant and non-trivial effects that depend on the orientation of the nanotube. The systematic series of calculations from our lab may be useful in understanding the transport of functionalized nanoparticles through lipid membranes as one of the determinants of bioavailability and toxicity. References: W.F.D. Bennett, J.L. MacCallum, D.P. Tieleman. 2009. Thermodynamic analysis of the effect of cholesterol on dipalmitoylphosphatidylcholine lipid membranes., J. Am. Chem. Soc. 131, pp.1972-1978. J. Wong-Ekkabut, S. Baoukina, W. Triampo, I-M. Tang, D.P. Tieleman, L. Monticelli. 2008. Computer simulation study of fullerene translocation through lipid membranes, Nature Nanotechnology 3, pp. 363 – 368 J.L. MacCallum, D.P. Tieleman. 2008. Interactions between small molecules and lipid bilayers, Curr. Top. Memb. 60, pp. 227-256 J.L. MacCallum, W.F. D. Bennett, D. P. Tieleman. 2008. Distribution of Amino Acids in a Lipid Bilayer from Computer Simulations, Biophys. J. 94, pp. 3393-3404
      Speaker: Prof. Peter Tieleman (University of Calgary, Canada)
    • 12:00 PM 12:45 PM
      Natural organic material characteristics affect the environmental behavior of manufactured nanoparticles 45m
      Rapid development and expansion of nanotechnology and growing use of nano-products have raised numerous safety concerns among the public and scientific community. Potential release of nanoparticles (NPs) into the environment is predictable through point and/or non-point sources. Environmental parameters such as pH, ionic strength, and natural organic material (NOM) profoundly affect their environmental behavior in aquatic systems. This in turn will influence the biological interaction and potential toxicity of NPs in the environment. In this study we examined how the physico-chemical characteristics of NOM affect the colloidal behavior of C60 fullerene and α-aluminum oxide NPs as two model NPs. Three structurally different humic acids and tannic acid were used as model NOMs. Aggregation behavior of NPs and structural characterizations of the adsorbed NOM on Al2O3 NPs were studied using DLS, AFM, TEM and DRIFT techniques. Fullerene suspension had a negatively charged surface over a wide range of pH, while Al2O3 had pH dependent charge with ZPC of 7.9. Surface charge of pure fullerene suspension decreased to more negative values after addition of any type of NOM, leading to a more stable colloidal system. Surface charge of Al2O3 NPs also decreased with the addition of NOM, which enhanced the colloidal stability at pH near or above its ZPC. However, below ZPC the presence of free NOM decreased stability of the colloidal Al2O3 system due to charge neutralization as well as bridging flocculation. Early stage aggregation kinetics studies were conducted by addition of varying concentrations of Ca2+ to the NPs suspensions. Addition of Ca2+ to the fullerene + NOM and the NOM-coated Al2O3 NPs systems increased zeta potential almost uniformly for all types of NOM. Critical coagulation concentration (CCC) was calculated for each NP and NOM pair combination. The CCCs increased with increasing molecular weight and decreasing polarity of NOM. Our data clearly showed that high molecular weight NOMs promoted the colloidal stability of fullerene + NOM system and the NOM-coated Al2O3 NPs through steric stabilization. This is in agreement with the DRIFT spectra of NOM-coated Al2O3 NPs showing higher aliphatic content in the complexes prepared with high molecular weight NOMs. However, low molecular weight NOMs also enhanced colloidal stability of fullerene and NOM-coated Al2O3 NP suspensions but mainly through electrostatic repulsion. In contrast to NOM-coated Al2O3 and fullerene systems, we observed that the presence of free long chain polymeric materials in NOM destabilized the colloidal suspension of pure Al2O3 NPs in acidic pHs. The plausible mechanism could be the coiling of long molecular chains of NOM followed by NPs entrapment. NPs aggregate size would be a determining factor in their fate, mobility and sedimentation in aqueous systems, which will consequently affect their biological interactions. This study highlights the effect of physico-chemical characteristics of NOM on the aggregation of NPs through modification of their surface properties.
      Speaker: Prof. Baoshan Xing (University of Massachusetts, USA)
    • 12:45 PM 2:15 PM
      Lunch 1h 30m
    • 2:15 PM 3:00 PM
      Engineered nanoparticles in plants 45m
      With the rapid development of nanotechnology engineered nanoparticles will eventually enter the environment. The interactions between engineered nanoparticles with naturally organic molecules, aquatic organisms, and plant species determine the fate of these nanoparticles in ecological systems and the food chain, and present vast new opportunities for multidisciplinary research. In this presentation, the effects of adsorption of semiconducting quantum dots on the photoactivities of algae, one type of single-celled plants, will be discussed. The solubility of carbon-based nanoparticles, from fullerene C70 to multiwalled carbon nanotubes, will be compared in natural organic matter with respect to their morphology. Using rice and pepper plants as model systems, experimental results showing the uptake, translocation and generational transmission of fullerene C70 will be presented.
      Speaker: Mr Sijie Lin (Clemson University, USA)
    • 3:00 PM 3:30 PM
      Coffee & tea 30m
    • 3:30 PM 4:15 PM
      Free energy of nano-pore formation and growth in membranes 45m
      The free energy cost for creating water filled pores of different sizes in model membranes is discussed and calculated from molecular dynamics simulations. Clearly the free energy cost for creating a hydrophilic pore with the lipid head groups turned inwards towards that water is less than that for creating a hydrophobic pore with hydrocarbon towards the water. This depends, however, on the ratio between bending modulus and surface tension and one might think of systems in which the hydrophobic pore is more stable. There are also systems for which a vacuum pore would be more stable than the water filled one. The free energy was calculated from atomistic molecular dynamics simulations as a function of a reaction coordinate using a constraining potential. The free energy profile that came out of the simulations is quadratic for a radii less than about 0.3 nm, and linear shape for larger radii. In the outer region, a line tension can be calculated that is consistent with experimentally measured values. Further, this line tension can be rationalized and understood in terms of the bending energy to deform the bilayer. The region with small radii can be described and understood in terms of statistical mechanics of density fluctuations. In the region of cross over between a quadratic and linear free energy there was some hysteresis associated with filling and evacuation of the pore with water. The meta-stable pre-pore state hypothesized to interpret experiments was not observed in this region. Reference: Free energy of a trans-membrane pore calculated from atomistic molecular dynamics simulations, J. Wohlert, W.K. den Otter, O. Edholm and W. J Briels, J. Chem. Phys. 124(2006) 154905.
      Speaker: Prof. Olle Edholm (Royal Institute of Technology KTH, Sweden)
    • 4:15 PM 5:00 PM
      Discussion 45m
      Speaker: Prof. Ilpo Vattulainen (Dept of Physics, Tampere Univ of Tech)
    • 5:00 PM 5:15 PM
      Closing 15m
      Speaker: Prof. Ilpo Vattulainen (Dept of Physics, Tampere Univ of Tech)