Challenges in modeling and simulations of nanoparticles in complex environments

May 29, 2019 to May 31, 2019
Location : CECAM-IT_SIMUL, Italian Institute of Technology - Genoa, Italy


  • Zoe Cournia (Academy of Athens, Greece)
  • Adam Pecina (Istituto Italiano di Tecnologia, Italy)
  • Marco De Vivo (Istituto Italiano di Technologia, Italy)



   Nanoscale Advances

   Journal of Chemical Information and Modeling

   Nanoscale Horizons

   RSC Nanoscale

   Journal of Chemical Theory and Computation


Practical information: 

The deadline for registration is April 12th (with final answers given on April 30th)

Our workshop will host ~20 invited talks of 35 min (including Q&A). In addition, there will be a poster session, and a few slots (~5) for short talks of ~25 min (to be chosen from abstracts). If you would like to present your results, please mention your preferred format (contributed talk or poster) with your application. 


 State of the art

Nanoparticles have technological applications in a variety of fields, from material science to medicine.[1-8] The functionality of a nanoparticle is determined by its chemical structure, which can have complex mixtures of sizes and shapes. In addition, most nanoparticles feature a coating layer of organic molecules that strongly affect their properties and functionality. Importantly, these molecules forming the coating monolayer regulate self-organization, dispersion, solvation, solubility, and other crucial properties. As such, these molecules can be exploited to produce cooperative chemical systems capable of recognizing, signaling, interacting with, and transforming other entities.[9,10] Therefore, understanding nanoparticle-environment interactions (solvent, matrix, membranes etc.) is crucial when developing nanoparticle-based applications for human health and technology. However, there is still very poor understanding of the fundamental nanoparticle’s behavior, particularly at the level of the outer coating monolayer.[11]

Properties such as size, shape, and surface are therefore of intrinsic importance with regard to the nanoparticle interactions with complex environments such as the cell matrix and drug delivery.[12-14] The challenge is now to understand how different nanoparticles form, and how their chemistry mediates function and toxicity, and nanoparticle-membrane interactions. In this scenario, computational modeling and simulations, integrated with experiments, is a powerful approach to increase our atomic-level understanding of the fundamental nanoparticle structure and behavior. Multiscale computational simulations, spanning from ab initio simulations to classical molecular dynamics simulations, can clarify the organization and interaction of the coating molecules. For this reason, our workshop will focus on the current challenges in computational simulations of nanoparticles, including their functionalization, from catalysis (nanozymes) to membrane interacting nanoparticles. In addition, the workshop will take advantage of several experimentalists working on nanoparticles interacting with materials and biological environment. Ultimately, we will discuss and debate how computational methods can further evolve to build novel tools for a deeper understanding of nanostructures and nanomaterials.


 Workshop organization

Our workshop will focus mainly on the methodological improvements for studying nanoparticles and their interaction with complex realistic environments, including protein membranes. We will discuss our models and approaches with experimentalists throughout following sessions:


  1. Nanoparticles and membranes

The increasing applications of nanoparticles in a variety of products, ranging from drug and gene delivery materials to consumer goods like paints, require that these engineered nanomaterials will come in contact with human cells without damaging essential tissues. Before nanoparticles contact healthy human cells, their cytotoxicity needs to be thoroughly evaluated and quantified in order to assess potential health risks. However, current toxicological knowledge about nanoparticles is extremely limited and traditional toxicology does not allow for a complete understanding of the size, shape, composition and aggregation-dependent interactions of nanostructures with biological systems. Efficient delivery must be achieved while avoiding cytotoxicity during passage through cell membranes to reach intracellular target compartments. Intracellular uptake of a nanoparticle may induce phase transitions, restructuring, stretching, or even complete disruption of the membrane. Therefore, assessment of the therapeutic and/or toxic effects of nanoparticles on biological cells requires a thorough understanding of the mechanisms with which nanoparticles interact with the cell membrane. An understanding of the relationship between the physico-chemical properties of NPs and the in vitro behavior would provide a basis for assessing toxic response and more importantly could lead to predictive models for estimating toxicity. The nanoparticles can interact with, and penetrate through biomembranes in a similar way as globular proteins. For example, it is known that the binding can be influenced by the charges on the nanoparticles surface. The molecular mechanism of interaction/absorption/permeation is however not known yet. Computational modeling can provide unprecedented insights into such processes in detail that is not accessible by experiments. We will thus focus here on the insights that can be generated by coarse-grained models and force-field parameters for atomistic molecular dynamics (MD), as well as enhanced sampling methods for free-energy calculations, such as metadynamics and accelerated MD either in explicit or implicit environments.


  1. Functionalized Nanoparticles

Over the last few years, several studies have shown that the nanoparticles, e.g. monolayer-protected gold nanoparticles (MPGNs), can be functionalized to produce nanodevices with unique properties. As mentioned before, the molecules forming the coating monolayer are the main contributor to the nanoparticle’s functionality. Recently, Riccardi et al.[11] have shown how the self-organized nature of the complex and flexible coating monolayer of MPGNs dictates its structure and function resembling that of proteins. There is however a very poor understanding of the fundamental nanoparticle’s behavior particularly on the level of monolayered surface. Moreover, it has been shown that such functionalized nanoparticles can have catalytic functions, too. The mechanism of these nanozymes is facilitated by metal ions chelated by the coating molecules of MPGNs, mimicking the two-metal-ion mechanism of metalloenzymes. Multiscale approaches will likely affect the rational-driven nanoparticle design, as they did already in the case of metal-dependent drug design. 

Here, we will discuss how multiscale simulations to investigate the structure, dynamics, and mechanism of action of functionalized nanoparticles. We will examine the role of calculations of different level of theory. For example, we will analyze how ab initio QM, DFT, and semiempirical (SQM) methods can elucidate nanoparticle’s physico-chemical features and overall dynamical behavior.


  1. Experiments meet simulations for nanoscience

Here, we will focus on how experimental measurements are used to clarify nanoparticle’s properties, and how are these measures integrated with insights from computations. For example, Rastrelli et al.[15] have developed a novel NMR-based approach to detect specific analyte in solution. Other methods span from TEM, microscopy, kinetics measurements of nanozymes, and more. We will discuss here how these experiments can be fully integrated with calculations at different levels of theory to better understanding the properties and function of nanoparticles.


  1. Nanoparticles for health and technology

Nanoparticles offer the potential to improve human health and welfare, environment and product performance in general. In this session, we will discuss the development of active nanodevices with a wide range of application in nanomedicine, from diagnostic technologies to therapies. For example, we will examine the challenges and advantages of the modeling of nanocarriers that can deliver in targeted drugs, also increasing their therapeutic activities and reducing their side effects. The use of nanoparticles holds promise also in the energy technology. We will examine here the computations of nanoparticles involved in all kinds of nanoscale processes, e.g. energy conversion, transport, and storage. 




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(4) Su, S. et al. Nanoscale 2013, 5, 2589.
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