Tag Archives: University College Dublin

Systems biology and nanoinformatics

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A May 29, 2023 news item on Nanowerk announces research from an international research team focused on a new nanoinformatics approach, Note: Links have been removed,

Researchers have discovered a new response mechanism specific to exposure to nanoparticles that is common to multiple species. By analysing a large collection of datasets concerning the molecular response to nanomaterials, they have revealed an ancestral epigenetic mechanism of defence that explains how different species, from humans to simpler creatures, adapt to this type of exposure.

The project was led by Doctoral Researcher Giusy del Giudice and Professor Dario Greco at the Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, Finland, in collaboration with an interdisciplinary team from Finland, Ireland, Poland, UK, Cyprus, South Africa, Greece and Estonia [emphasis mine] – including Associate Professor Vladimir Lobaskin from UCD School of Physics, University College Dublin, Ireland.

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A May 29, 2023 University College Dublin (UCD) press release, which originated the news item, delves further into the research, Note: Links have been removed,

Director of FHAIVE, Professor Greco said: “We have demonstrated for the first time that there is a specific response to nanoparticles, and it is interlinked to their nano-properties. This study sheds light on how various species respond to particulate matters in a similar manner. It proposes a solution to the one-chemical-one-signature problem, currently limiting the use of toxicogenomic [sic] in chemical safety assessment.”

Systems Biology meets Nanoinformatics

Associate Professor Vladimir Lobaskin, who is an expert in nanostructured biosystems, said: “In this major collaborative work, the team led by the University of Tampere and including UCD School of Physics not only discovered common responses to nanoparticles across all kinds of organisms from plants and invertebrates to humans but also common features of nanomaterials triggering those responses.”

He said: “Tens of thousands of novel nanomaterials reach the consumer market annually. It is an enormous task to screen them all for possible adverse effects to protect the environment and human health. It could be damage to the lung when we inhale dust, a release of toxic ions by dust particles, production of reactive oxygen species, or binding of the cell membrane lipids by nanoparticles. In other words, it all starts with relatively simple physical interactions at the surface of the nanoparticles that are usually not known to biologists and toxicologists but needed to understand what we should fear when exposed to nanomaterials.”

In the past decade, OECD [Organisation for Economic Cooperation and Development] countries have adopted a mechanism-aware toxicity assessment strategy based on the Adverse Outcome Pathway analysis establishing causal relationships between biological events leading to a disease or negative effect on the population. Once the Adverse Outcome Pathway is determined, one can trace the chain of biological events back to the origin – the molecular initiating event that triggered the cascade.

Attempts of statistical analysis of the toxicology data of recent years have not succeeded in identifying the nanomaterial properties responsible for the adverse outcomes. The problem is that the material characteristics typically provided by the producers, such as nanoparticle chemistry and size distribution, are too basic and insufficient to make sensible predictions of their biological activity.

An earlier work, co-authored by the UCD School of Physics team, suggested the collection of advanced descriptors of nanomaterials, using computational materials science if necessary, to understand the interactions of nanoparticles with biological molecules and tissues and enable the prediction of the molecular initiating events. These advanced descriptors can provide the missing bits of information and include the materials’ dissolution rates, the polarity of the surface atoms, molecular interaction energies, shape, aspect ratios, indicators of hydrophobicity, amino acid or lipid binding energy – as well as anything that may cause disruption of the normal cell or tissue functions.

Associate Professor Lobaskin and colleagues at UCD Soft Matter Modelling Lab have been working on in silico materials’ characterisation and evaluated the descriptors that correlate with the hazardous potential of nanoparticles.

He said: “In the analysis presented in this latest Nature Nanotechnology paper, we for the first time were able to see what is in common between different materials associated with the health risks at the molecular level. This publication is the first demonstration of the power of nanoinformatics, a new field of research extending the ideas from cheminformatics and bioinformatics, and also a big promise: using digital twins of materials created on a computer will soon enable us to screen and optimise novel materials for safety and functionality even before they are produced to make them safe and sustainable by design.”

Here’s a link to and a citation for the paper,

An ancestral molecular response to nanomaterial particulates by G. del Giudice, A. Serra, L. A. Saarimäki, K. Kotsis, I. Rouse, S. A. Colibaba, K. Jagiello, A. Mikolajczyk, M. Fratello, A. G. Papadiamantis, N. Sanabria, M. E. Annala, J. Morikka, P. A. S. Kinaret, E. Voyiatzis, G. Melagraki, A. Afantitis, K. Tämm, T. Puzyn, M. Gulumian, V. Lobaskin, I. Lynch, A. Federico & D. Greco. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01393-4 Published: 08 May 2023

This paper is open access.

Environment influences nanomaterial reactions to biological cells

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The discussion I’ve seen around nanomaterials and toxicological effects has largely centered on shapes, size, aggregate/agglomerate, etc. By contrast, Carl Walkey’s July 24, 2012 Nanowerk Spotlight essay focuses on nanomaterial surfaces, bare or coated with serum proteins (Note: I have removed links),

Biomolecule adsorption to nanomaterials is usually studied from physiological fluids with suspended biomolecules. Examples include blood serum/plasma, pulmonary surfactant, and synovial fluid. However, until now the amount of those molecules has not been considered relevant to the study. In a recent article appearing in ACS Nano (“Effects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells”), Drs. Anna Salvati, Kenneth Dawson, and their colleagues at the University College in Dublin, Ireland, show that if nanoparticles are exposed directly to cells in the absence of suspended biomolecules, the nanoparticles will extract biomolecules directly from cells themselves.

In their experiments, the team exposed silica nanoparticles to cells in two sets. One set was introduced into cell culture media that was supplemented with the usual concentration of fetal bovine serum, and the other into media that had no serum additives. They then incubated both sets of particles with a lung cancer cell line and measured particle uptake kinetics and cell adhesion. Nanoparticles treated under both conditions associated with cells. However, the particles that were incubated in media alone associated to a much greater extent than those that were first incubated in serum. This indicates that the affinity of the bare nanoparticle surface to the cell is much higher than the affinity of an equivalent surface that is coated with serum proteins. [emphasis mine] Similar observations are reported before for other systems, where it was also found that uptake under serum-free conditions is higher.

Moe specifically,

“When the nanomaterial is put in contact with a physiological environment, it is given a menu of possible biomolecules to adsorb” explains Dawson. “It will essentially go shopping for the biomolecules that it wants. Over time, it will exchange with the environment until it finds the things that it really likes most. If you don’t give it enough biomolecules in the form of serum, it will extract components from the cells themselves.”

The same silica nanoparticles exposed to cells in the two different conditions had different cellular responses as well. Most of the serum-coated particles were taken up within vesicles in the cell cytoplasm and produced no overt signs of toxicity. In contrast, the particles without a serum coating adhered to the cell surface to a greater extent, were present in vesicles, and some were also found free-floating in the cytoplasm. Exposure to particles in absence of serum significantly decreased cell viability and caused cells to take on a rounded morphology that is indicative of cell death. Dawson believes that cell death from uncoated particles is the result of strong interactions between the particle surface and the cell surface, which may damage the cell membrane, and/or initiate aberrant signaling cascades. When serum proteins are adsorbed to the nanoparticles, they ‘passivate’ the surface and limit direct nanomaterial-cell interactions.

When considering the early interactions of a nanomaterial with a cell, Dawson points out that one cannot think of the nanomaterial alone. Instead, one must think of the nanoparticle and its adsorbed biomolecules as a fundamental unit. [emphasis mine]

Most importantly,

Dawson believes that researchers must pay closer attention to the composition of the biomolecular environment surrounding the particles and cells when performing in vitro experiments. In other words, it is as important to consider the composition of the biomolecules in the media as it is to consider the chemical nature of the nanoparticle and the cell type. [emphasis mine]

“What’s absolutely clear is that depending on the type of dispersion that you make up, whether you add 10% serum or 20% serum, you get different levels of cell uptake” says Dawson. “Indeed, you get different levels of damage as well. It is therefore not meaningful to say that the nanoparticle is or is not toxic in that simplistic way. You can make a material toxic if you really want to make it toxic. You can make many materials damage cells simply because these have high surface energy. However, in a realistic physiological environment, part of the particle surface is covered and so that kind of damage would not be applicable.”

I encourage anyone who’s interested in nanotoxicology to read Walkey’s essay in full as I’ve excerpted only a portion.

BTW, Carl Walkey is a PhD graduate student at the University of Toronto and a member of the Integrated Nanotechnology & Biomedical Sciences Laboratory (INBS). I last mentioned Walkey in my July 12, 2012 posting about his Nanowerk Spotlight essay on nanotoxicology and animal studies.