Exploring the interaction of 2D materials and biological systems with Valentina Castagnola

The manipulation and complete exploitation of graphene materials in a biological context can open up unexpected opportunities in biomedicine. In this interview, Valentina Castagnola explains how her work has focused on understanding what happens when graphene comes in contact with biomolecules and cells. Castagnola works as a researcher at the Graphene Flagship Partner Italian Institute of Technology (IIT), Center for Synaptic Neuroscience and Technology, under the guidance of Prof. Fabio Benfenati, where she directs a group of early-career scientists and students, dedicated to exploring how functional nanomaterials interact with both the central and peripheral nervous systems.

How did you first become interested in your current research project?

Since my first University internship, I have developed an ever-growing passion for tackling problems and scientific questions. However, I soon realized that the thing I loved the most was that whenever you find a solution or an answer, a number of further scientific questions arise. The science-fiction writer, Ursula Le Guin once said “when you light a candle, you also cast a shadow.” This fascinating loop process captivates me, and I cannot help but perpetuate it.

During my first postdoctoral experience in 2015 at the Graphene Flagship Partner University College Dublin (UCD), I became a Graphene Flagship fellow and embarked on a journey exploring the detailed biological interactions of colloidal graphene materials intended for biological applications. My lab at UCD was directed by Kenneth Dawson, who is the father of the concept of “protein corona,” which refers to how proteins in the blood spontaneously interact with nanomaterials and guide their biological fate. When I joined IIT in 2019, I continued my investigation, thanks in part to a precious collaboration with Andrea Armirotti at IIT’s Analytical Chemistry Lab, allowing me to delve even deeper into my research.

I was inspired by exceptional people I have encountered in my life and every step of my path was important in my personal and professional development to bring me here, exactly where I want to be.

Please can you describe the goals of your research?

First of all, I needed to find a form of graphene compatible with the biological environment:  graphene is a very hydrophobic material, meaning that it has a low affinity for water, which is, of course, the main component of all biological fluids. My first work at UCD aimed at producing graphene dispersions in a water-based solvent, exploiting ultrasound to separate the graphene layers from graphite, and the proteins present in the blood to generate a coat around the graphene surface that would make it stable in the biological environment.

During the development of this technology, I realized that some of the proteins composing the serum had a specific preferential affinity for the graphene surface. I then investigated how these specific proteins influence, guide, and mediate the interaction of graphene with cells and cell receptors. Once coated by proteins, it is as if these materials possess a set of “keys” to open determined biological locks. To understand the molecular details of these “keys” (therefore possible “lock picking”), with the help of Andrea Armirotti, we developed a methodology to identify the molecular motifs that are available at the periphery of the protein coat – the most exposed parts of the protein corona, the real key features.

Besides proteins, I also looked at the role of other biomolecules in the blood, such as lipids, that might play a fundamental role in this lock-and-key process and have been so far largely overlooked.  

Supported by a growing bio-corona community, I believe that implementing improved protocols for bio-nano interactions studies will unlock the potential of nanomedicine for the treatment of several burdensome diseases in our society.

Why do you feel your research is important, and what benefits could it bring to society?

There is a growing effort to provide alternatives to animal models and develop advanced models that mimic different biological contexts, such as organoids, organs-on-chip, 3D cultures, and in silico simulations, among others. This direction is clear in science worldwide, although achieving sufficiently trustworthy data to replace animal tests will require significant effort.

In the field of nanomedicine – the use of nanosized materials for therapy and diagnosis – we have known for several years that complex interactions at the nanoscale between artificially engineered functional materials and biological molecules, from metabolites and lipids to proteins and cells, result in a considerable mismatch between in vitro and in vivo results. With my colleagues at IIT, I am gaining an in-depth understanding of how bio-nano interactions take place in vivo, and translating this knowledge into realistic in vitro models. This is fundamental if we aim to replace in vivo testing.

What are your plans for the future?

Recently, I have explored how graphene interacts with the brain's protection, known as the blood-brain barrier. Indeed my research  is now focused on developing alternative therapeutics for neurodegenerative diseases using hybrid nanotechnological tools and I am keen on identifying new materials able to reach the brain. The topic of neurodegeneration is a source of great motivation for me, both professionally and personally. My desire is to apply my knowledge, training, and passion to serve this purpose, with the hope of making even a small step forward that could one day make a significant difference for patients suffering from these conditions and their families.

Additionally, I am committed to passing on my passion, ambition, and dedication to the younger scientists who work with me. I believe it is the responsibility of every scientist to foster this positive attitude and share their enthusiasm with others. I am so happy to see my group working hard with great harmony, determination, and passion toward a common objective of understanding, scientific rigor, excellence and creativity. Science, for me, is a collective effort.

References

Castagnola, Valentina, et al. "Interactions of Graphene Oxide and Few-Layer Graphene with the Blood–Brain Barrier." Nano Letters 23.7 (2023): 2981-2990. https://pubs.acs.org/doi/10.1021/acs.nanolett.3c00377

Castagnola, Valentina, et al. "Biological recognition of graphene nanoflakes." Nature communications 9.1 (2018): 1577. https://www.nature.com/articles/s41467-018-04009-x

Liessi, Nara, et al. "Isobaric labeling proteomics allows a high-throughput investigation of protein corona orientation." Analytical chemistry 93.2 (2020): 784-791. https://pubs.acs.org/doi/10.1021/acs.analchem.0c03134

Alnasser, Fatima, et al. "Graphene nanoflake uptake mediated by scavenger receptors." Nano Letters 19.2 (2019): 1260-1268. https://pubs.acs.org/doi/10.1021/acs.nanolett.8b04820

Braccia, Clarissa, et al. "The lipid composition of few layers graphene and graphene oxide biomolecular corona." Carbon 185 (2021): 591-598. https://www.sciencedirect.com/science/article/pii/S000862232100943X?via%3Dihub