Tag Archives: SISSA (Scuola Internazionale Superiore di Studi Avanzat)

A carbon nanotube ‘bridge’ for nerves

Italian researchers have developed a three-dimensional carbon nanotube sponge (or bridge) that could be used in conjunction with neural explants according to a July 15, 2016 SISSA press release (also on EurekAlert), which describes the work,

A complex study, lasting several years and involving work groups with specialties in various fields, has shown that a new material (a three-dimensional sponge made of carbon nanotubes) supports the growth of nerve fibers, bridging segregated neural explants and providing a functional re-connection. The study, which was coordinated by the International School for Advanced Studies (SISSA) in Trieste, in collaboration with the University of Rome Tor Vergata and the University of Trieste, also observed biocompatibility in vivo of the material, demonstrating that implanting it into  the brain of small rodents does not cause large scars or a marked immune response.

“Under the microscope, it looks like a knotted tangle of tubes. It was initially studied by Maurizio De Crescenzi’s team at the University of Rome Tor Vergata for cleaning up spilled hydrocarbons in the sea,” explains Laura Ballerini, SISSA Professor and coordinator of the recently-published study. It was Maurizio Prato’s intuition, however, that pushed them to investigate the possibility of applying such a material to nerve tissue. The idea of developing the hybrids of neurons and nano-materials was the result of a long-term project and collaboration between Prato (University of Trieste) and Ballerini’s (SISSA) groups.

In the present study, Ballerini and her team first investigated the material’s reaction to nerve tissue in vitro. “We explanted two spinal cord segments and cultured them together but separated by 300 microns,” says Sadaf Usmani, a PhD student at the School and first author of the study. “In those conditions, without any scaffolds reconstructing the space between the two explants, we observed growth of nerve fibers which extended in a straight bundles in any direction, but not necessarily towards the other tissue. If we insert a small piece of the carbon sponge into the space between the two, however, we see dense growth of nerve fibers that fill the structure and intertwine with the other sample.”

“Observing fiber reaching the contralateral explant is not enough, however,” points out University of Trieste researcher and one of the authors of the study, Denis Scaini. “You have to show that there is a functional connection between the two populations of neurons.” For this, SISSA Professor, David Zoccolan and his team’s contribution was crucial. “With signal analysis techniques they had already developed, we were able to demonstrate two things: first, that spontaneous nervous activity in the two samples was actually correlated, indicating a connection, that was not there when the sponge was absent, and second,, that by applying an electrical signal to one of the samples, the activity of the second sample could be triggered, but only when the nanotubes were present.”

Tests for Biocompatibility

The results in the lab were extremely positive. But this was not sufficient for Ballerini and her colleagues. “In order to continue to invest additional energy and resources to the study for potential applications, is crucial to test if the material is accepted by living organisms without negative consequences,” says Ballerini.

To perform these tests, Ballerini’s team worked closely with SISSA Post-Doc researcher, and member of Zoccolan’s team, Federica Rosselli. “We implanted small portions of the material into the brain of healthy rodents. After four weeks, we observed that the material was well tolerated. There were limited scars, as well as low immune responses, some biological indicators even showed that there could be positive implications. There was also a progressive invasion of neurons within the sponge. The rats were vital and healthy during the entire four weeks,” says Usmani.

“In conclusion,” says Ballerini, “the excellent results at the structural and functional level in vitro and in vivo showed biocompatibility are encouraging us to continue this line of research. These materials could be useful for covering electrodes used for treating movement disorders like Parkinson’s because they are well accepted by tissue, while the implants being used today become less effective over time because of scar tissue. We hope this encourages other research teams with multidisciplinary expertise to expand this type of study even further.”

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

3D meshes of carbon nanotubes guide functional reconnection of segregated spinal explants by Sadaf Usmani, Emily Rose Aurand, Manuela Medelin, Alessandra Fabbro, Denis Scaini, Jummi Laishram, Federica B. Rosselli, Alessio Ansuini, Davide Zoccola1, Manuela Scarselli, Maurizio De Crescenzi, Susanna Bosi, Maurizio Prato, and Laura Ballerini. Science Advances  15 Jul 2016: Vol. 2, no. 7, e1600087 DOI: 10.1126/sciadv.1600087 Published 01 July 2016

This paper is open access.

H/t July 15, 2016 news item on phys.org.

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.

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.