Tag Archives: SISSA (International School for Advanced Studies)

Carbon nanotubes to repair nerve fibres (cyborg brains?)

Can cyborg brains be far behind now that researchers are looking at ways to repair nerve fibers with carbon nanotubes (CNTs)? A June 26, 2017 news item on ScienceDaily describes the scheme using carbon nanotubes as a material for repairing nerve fibers,

Carbon nanotubes exhibit interesting characteristics rendering them particularly suited to the construction of special hybrid devices — consisting of biological issue and synthetic material — planned to re-establish connections between nerve cells, for instance at spinal level, lost on account of lesions or trauma. This is the result of a piece of research published on the scientific journal Nanomedicine: Nanotechnology, Biology, and Medicine conducted by a multi-disciplinary team comprising SISSA (International School for Advanced Studies), the University of Trieste, ELETTRA Sincrotrone and two Spanish institutions, Basque Foundation for Science and CIC BiomaGUNE. More specifically, researchers have investigated the possible effects on neurons of the interaction with carbon nanotubes. Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. This result, which shows the extent to which the integration between nerve cells and these synthetic structures is stable and efficient, highlights the great potentialities of carbon nanotubes as innovative materials capable of facilitating neuronal regeneration or in order to create a kind of artificial bridge between groups of neurons whose connection has been interrupted. In vivo testing has actually already begun.

The researchers have included a gorgeous image to illustrate their work,

Caption: Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. Credit: Pixabay

A June 26, 2017 SISSA press release (also on EurekAlert), which originated the news item, describes the work in more detail while explaining future research needs,

“Interface systems, or, more in general, neuronal prostheses, that enable an effective re-establishment of these connections are under active investigation” explain Laura Ballerini (SISSA) and Maurizio Prato (UniTS-CIC BiomaGUNE), coordinating the research project. “The perfect material to build these neural interfaces does not exist, yet the carbon nanotubes we are working on have already proved to have great potentialities. After all, nanomaterials currently represent our best hope for developing innovative strategies in the treatment of spinal cord injuries”. These nanomaterials are used both as scaffolds, a supportive framework for nerve cells, and as means of interfaces releasing those signals that empower nerve cells to communicate with each other.

Many aspects, however, still need to be addressed. Among them, the impact on neuronal physiology of the integration of these nanometric structures with the cell membrane. “Studying the interaction between these two elements is crucial, as it might also lead to some undesired effects, which we ought to exclude”. Laura Ballerini explains: “If, for example, the mere contact provoked a vertiginous rise in the number of synapses, these materials would be essentially unusable”. “This”, Maurizio Prato adds, “is precisely what we have investigated in this study where we used pure carbon nanotubes”.

The results of the research are extremely encouraging: “First of all we have proved that nanotubes do not interfere with the composition of lipids, of cholesterol in particular, which make up the cellular membrane in neurons. Membrane lipids play a very important role in the transmission of signals through the synapses. Nanotubes do not seem to influence this process, which is very important”.

There is more, however. The research has also highlighted the fact that the nerve cells growing on the substratum of nanotubes, thanks to this interaction, develop and reach maturity very quickly, eventually reaching a condition of biological homeostasis. “Nanotubes facilitate the full growth of neurons and the formation of new synapses. This growth, however, is not indiscriminate and unlimited since, as we proved, after a few weeks a physiological balance is attained. Having established the fact that this interaction is stable and efficient is an aspect of fundamental importance”. Maurizio Prato and Laura Ballerini conclude as follows: “We are proving that carbon nanotubes perform excellently in terms of duration, adaptability and mechanical compatibility with the tissue. Now we know that their interaction with the biological material, too, is efficient. Based on this evidence, we are already studying the in vivo application, and preliminary results appear to be quite promising also in terms of recovery of the lost neurological functions”.

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

Sculpting neurotransmission during synaptic development by 2D nanostructured interfaces by Niccolò Paolo Pampaloni, Denis Scaini, Fabio Perissinotto, Susanna Bosi, Maurizio Prato, Laura Ballerini. Nanomedicine: Nanotechnology, Biology and Medicine, DOI: http://dx.doi.org/10.1016/j.nano.2017.01.020 Published online: May 25, 2017

This paper is open access.

Calming a synapse (part of a neuron) with graphene flakes

As we continue to colonize our own brains, there’s more news of graphene and neurons (see my Feb. 1, 2016 post featuring research from the same team in Italy featured in this post). A May 10, 2016 news item on ScienceDaily highlights work that could be used for epilepsy,

Innovative graphene technology to buffer the activity of synapses– this is the idea behind a recently-published study in the journal ACS Nano coordinated by the International School for Advanced Studies in Trieste (SISSA) and the University of Trieste. In particular, the study showed how effective graphene oxide flakes are at interfering with excitatory synapses, an effect that could prove useful in new treatments for diseases like epilepsy.

I guess the press release took a while to make its way through translation, here’s more from the April 10, 2016 SISSA (International School for Advanced Studies) press release (also on EurekAlert),

The laboratory of SISSA’s Laura Ballerini in collaboration with the University of Trieste, the University of Manchester and the University of Castilla -la Mancha, has discovered a new approach to modulating synapses. This methodology could be useful for treating diseases in which electrical nerve activity is altered. Ballerini and Maurizio Prato (University of Trieste) are the principal investigators of the project within the European flagship on graphene, a far-reaching 10-year international collaboration (one billion euros in funding) that studies innovative uses of the material.

Traditional treatments for neurological diseases generally include drugs that act on the brain or neurosurgery. Today however, graphene technology is showing promise for these types of applications, and is receiving increased attention from the scientific community. The method studied by Ballerini and colleagues uses “graphene nano-ribbons” (flakes) which buffer activity of synapses simply by being present.

“We administered aqueous solutions of graphene flakes to cultured neurons in ‘chronic’ exposure conditions, repeating the operation every day for a week. Analyzing functional neuronal electrical activity, we then traced the effect on synapses” says Rossana Rauti, SISSA researcher and first author of the study.

In the experiments, size of the flakes varied (10 microns or 80 nanometers) as well as the type of graphene: in one condition graphene was used, in another, graphene oxide. “The ‘buffering’ effect on synaptic activity happens only with smaller flakes of graphene oxide and not in other conditions,” says Ballerini. “The effect, in the system we tested, is selective for the excitatory synapses, while it is absent in inhibitory ones”

A Matter of Size

What is the origin of this selectivity? “We know that in principle graphene does not interact chemically with synapses in a significant way- its effect is likely due to the mere presence of synapses,” explains SISSA researcher and one of the study’s authors, Denis Scaini. “We do not yet have direct evidence, but our hypothesis is that there is a link with the sub-cellular organization of the synaptic space.”

A synapse is a contact point between one neuron and another where the nervous electrical signal “jumps” between a pre and post-synaptic unit. [emphasis mine] There is a small gap or discontinuity where the electrical signal is “translated” by a neurotransmitter and released by pre-synaptic termination into the extracellular space and reabsorbed by the postsynaptic space, to be translated again into an electrical signal. The access to this space varies depending on the type of synapses: “For the excitatory synapses, the structure’s organization allows higher exposure for the graphene flakes interaction, unlike inhibitory synapses, which are less physically accessible in this experimental model,” says Scaini.

Another clue that distance and size could be crucial in the process is found in the observation that graphene performs its function only in the oxidized form. “Normal graphene looks like a stretched and stiff sheet while graphene oxide appears crumpled, and thus possibly favoring interface with the synaptic space, ” adds Rauti.

Administering graphene flake solutions leaves the neurons alive and intact. For this reason the team thinks they could be used in biomedical applications for treating certain diseases. “We may imagine to target a drug by exploiting the apparent flakes’ selectivity for synapses, thus targeting directly the basic functional unit of neurons”concludes Ballerini.

That’s a nice description of neurons, synapses, and neurotransmitters.

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

Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks by Rossana Rauti, Neus Lozano, Veronica León, Denis Scaini†, Mattia Musto, Ilaria Rago, Francesco P. Ulloa Severino, Alessandra Fabbro, Loredana Casalis, Ester Vázquez, Kostas Kostarelos, Maurizio Prato, and Laura Ballerini. ACS Nano, 2016, 10 (4), pp 4459–4471
DOI: 10.1021/acsnano.6b00130 Publication Date (Web): March 31, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Feeling with a bionic finger

From what I understand one of the most difficult aspects of an amputation is the loss of touch, so, bravo to the engineers. From a March 8, 2016 news item on ScienceDaily,

An amputee was able to feel smoothness and roughness in real-time with an artificial fingertip that was surgically connected to nerves in his upper arm. Moreover, the nerves of non-amputees can also be stimulated to feel roughness, without the need of surgery, meaning that prosthetic touch for amputees can now be developed and safely tested on intact individuals.

The technology to deliver this sophisticated tactile information was developed by Silvestro Micera and his team at EPFL (Ecole polytechnique fédérale de Lausanne) and SSSA (Scuola Superiore Sant’Anna) together with Calogero Oddo and his team at SSSA. The results, published today in eLife, provide new and accelerated avenues for developing bionic prostheses, enhanced with sensory feedback.

A March 8, 2016 EPFL press release (also on EurekAlert), which originated the news item, provides more information about Sorenson’s experience and about the other tests the research team performed,

“The stimulation felt almost like what I would feel with my hand,” says amputee Dennis Aabo Sørensen about the artificial fingertip connected to his stump. He continues, “I still feel my missing hand, it is always clenched in a fist. I felt the texture sensations at the tip of the index finger of my phantom hand.”

Sørensen is the first person in the world to recognize texture using a bionic fingertip connected to electrodes that were surgically implanted above his stump.

Nerves in Sørensen’s arm were wired to an artificial fingertip equipped with sensors. A machine controlled the movement of the fingertip over different pieces of plastic engraved with different patterns, smooth or rough. As the fingertip moved across the textured plastic, the sensors generated an electrical signal. This signal was translated into a series of electrical spikes, imitating the language of the nervous system, then delivered to the nerves.

Sørensen could distinguish between rough and smooth surfaces 96% of the time.

In a previous study, Sorensen’s implants were connected to a sensory-enhanced prosthetic hand that allowed him to recognize shape and softness. In this new publication about texture in the journal eLife, the bionic fingertip attains a superior level of touch resolution.

Simulating touch in non-amputees

This same experiment testing coarseness was performed on non-amputees, without the need of surgery. The tactile information was delivered through fine, needles that were temporarily attached to the arm’s median nerve through the skin. The non-amputees were able to distinguish roughness in textures 77% of the time.

But does this information about touch from the bionic fingertip really resemble the feeling of touch from a real finger? The scientists tested this by comparing brain-wave activity of the non-amputees, once with the artificial fingertip and then with their own finger. The brain scans collected by an EEG cap on the subject’s head revealed that activated regions in the brain were analogous.

The research demonstrates that the needles relay the information about texture in much the same way as the implanted electrodes, giving scientists new protocols to accelerate for improving touch resolution in prosthetics.

“This study merges fundamental sciences and applied engineering: it provides additional evidence that research in neuroprosthetics can contribute to the neuroscience debate, specifically about the neuronal mechanisms of the human sense of touch,” says Calogero Oddo of the BioRobotics Institute of SSSA. “It will also be translated to other applications such as artificial touch in robotics for surgery, rescue, and manufacturing.”

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

Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans by Calogero Maria Oddo, Stanisa Raspopovic, Fiorenzo Artoni, Alberto Mazzoni, Giacomo Spigler, Francesco Petrini, Federica Giambattistelli, Fabrizio Vecchio, Francesca Miraglia, Loredana Zollo, Giovanni Di Pino, Domenico Camboni, Maria Chiara Carrozza, Eugenio Guglielmelli, Paolo Maria Rossini, Ugo Faraguna, Silvestro Micera. eLife, 2016; 5 DOI: 10.7554/eLife.09148 Published March 8, 2016

This paper appears to be open access.

Babies have more general physics knowledge than experts realized

A Feb. 10, 2016 news item on ScienceDaily sheds some light on babies and their knowledge of physics,

We are born with a basic grasp of physics, just enough not to be surprised when we interact with objects. Scientists discovered this in the past two decades. What they did not know yet was that, as early as five months of age, this ‘naive’ physics also extends to liquids and materials that do not behave like solids (for example, sand), as demonstrated by a new study.

A Feb. 10, 2016 SISSA (International School of Advanced Studies) press release (also on EurekAlert), which originated the news item, describes the conclusions and the research in more detail,

If we hold a ball and then let go of it and the ball remains suspended in mid-air, even a baby a few months old will be surprised. Just like an adult, the baby expects the ball to fall to the floor. Even at such a young age humans already have some rudimentary knowledge of the behaviour of solids. Now a new study extends this knowledge to add liquids and other non-solids to the “naïve physics” of infants.

“This new study developed out of previous experiments”, explains Alissa Ferry, SISSA research scientist and among the authors of the paper, “in which we observed that infants were surprised when a liquid failed to behave as a liquid (in those experiments we “cheated” by disguising solids as liquids)”. Their surprise, explains Ferry, demonstrates that their expectations for a liquid had not been met. “However, what we couldn’t establish was whether the infants knew how a liquid should behave or whether they just expected it to be different from a solid”.

Ferry and colleagues (the first author is Susan Hespos of Northwestern University in Illinois, USA, where the experiments were conducted) therefore devised a new set of tests with a greater range of materials and “interactions”. In a first “habituation” phase, the infants were shown the contents of a glass by tilting the glass in front of them. The glass either contained a solid (which, when not moving, had identical appearance to water) or some water. When the glass was tilted back and forth, the two materials behaved differently: the solid remained perfectly still whereas the water moved. This phase served to teach the infants whether they were looking at a solid or a liquid.

Next, the infants were shown an identical glass to the one seen in the previous phase (making them believe that it was the same glass) which contained either the material they had already seen or the other material. At this point, the infants watched the experimenter either pour the contents (liquid or solid) of the glass into another glass containing a grid or submerge the grid in the liquid (or rest it on top of the solid) inside the glass.

“In the previous experiments we merely poured the contents of the glass. This time we added a grid to find out whether the infants really understood the loose cohesiveness of liquids, which can pass through a perforated surface and recompose in the vessel unlike solids which, being highly cohesive, cannot pass through a grid” explains Ferry.

In the habituation phase, in fact, the infants could know how liquids change shape with movement, but it was unknown if they could use this knowledge to understand other properties of liquids, like loose cohesiveness. “If infants understand the properties of liquids, then they should be surprised when, what they think is a liquid gets trapped on a grid”.

And the analysis of the infants’ behaviour shows that when they expected a liquid they were surprised to see it blocked by the grid (or see the grid unable to penetrate the material). Conversely, if they thought they were looking at a solid, then they were surprised when they saw it pass through the grid.

The investigators also used other materials like sand and small glass spheres. “Even in these cases the infants showed that they knew the behaviour of substances”, concludes Ferry. “This is especially interesting because, while we can imagine that 5-month-old infants already have had extensive direct experience with liquids and especially water through meals, baths and 9 months in the amniotic liquid, it’s unlikely that they’ve had many encounters with sand or glass balls, suggesting that infants have a naïve understanding of the physics of nonsolid substances”.

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

Five-Month-Old Infants Have General Knowledge of How Nonsolid Substances Behave and Interact by Susan J. Hespos, Alissa L. Ferry, Erin M. Anderson, Emily N. Hollenbeck, anb Lance J. Rips. Psychological Science February 2016 vol. 27 no. 2 244-256 doi: 10.1177/0956797615617897 Published online: January 7, 2016

This paper is behind a paywall.

Atomic force microscopes, images, and friction

To me, this looks like the ‘batman’ symbol but it’s not.

Nanofriction at the tip of the microscope. Courtesy SISSA [Scuola Internazionale Superiore di Studi Avanzat], Italy

Nanofriction at the tip of the microscope. Courtesy SISSA [Scuola Internazionale Superiore di Studi Avanzat], Italy

Here’s more about the work that produced this image from a Dec. 17, 2013 news item on Azonano,

Atomic force microscopes are able to reproduce spectacular images, at the scale of single atoms. This is made possible by the oscillation of a very sharp probe tip over the surface being observed. The tip never touches the surface but gets so close to it, at distances in the order of one billionth of a metre, that it “feels” the force due to the interaction with the atoms making up the material being observed.

These are tiny forces, in the order of nanonewtons (meaning one billion times smaller than the weight of an apple). By measuring these forces one can reproduce an image of the material. A research group, which brings together experimental physicists from the University of Basel and theoretical physicists from SISSA, has observed and explained a peculiar effect, a source of “friction” in this type of nanoscopic observations.

The Dec. 16,  2013 SISSA (Scuola Internazionale Superiore di Studi Avanzat) press release, which originated the news item, provides more specific detail,

 When the tip of the microscope oscillates over certain surfaces, in this case over NbSe2 (niobium selenide), peaks of “dissipation” (i.e., loss of energy) can be seen when the tip is at specific distances from the surface, as if it were held back, at certain locations, by some frictional force. This effect, which is related to a property of the surface known as charge density waves (CDW), was experimentally observed by the Basel physicists and first explained by Franco Pellegrini, Giuseppe Santoro and Erio Tosatti, of SISSA, by means of a theoretical model analysed with the use of numerical simulations.

“Our model describes in detail the interaction between the tip of the atomic force microscope and the CDW,” explains Pellegrini. “The model reproduces – and predicts – the data observed experimentally”.

“Knowledge of nanofriction is important today. Progressive miniaturization of electronic devices makes it crucial to understand the mechanisms underlying energy losses, continues Pelligrini.

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

Giant frictional dissipation peaks and charge-density-wave slips at the NbSe2 surface by Markus Langer, Marcin Kisiel, Rémy Pawlak, Franco Pellegrini, Giuseppe E. Santoro, Renato Buzio, Andrea Gerbi, Geetha Balakrishnan, Alexis Baratoff, Erio Tosatti & Ernst Meyer. Nature Materials (2013) doi:10.1038/nmat3836 Published online 15 December 2013

This paper is behind a paywall although you can obtain a preview through ReadCube Access.