A bioelectronic platform allows to controlthe proliferation of tumour cellsand to record bioelectrical activity of the system.
Measurement and control of the proliferation of living cells using light pulses: we are in the field of bioelectronics, at the intersection of engineering, physics and biology. The latest frontier is to be able to selectively control the activity of living cells and tissues through light for therapeutic and diagnostic applications.
An international team of researchers, led by Tor Vergata University of Rome, via the work of electronic engineers and medical biologists, has created an optoelectronic bio-platform both for cell culture, under light stimulation (open architecture), and for the analysis of the bioelectrical signals of cells grown inside it (closed architecture), using a light-sensitive organic polymer semiconductor. The device, compact and easy to use, allows to control, through the use of light stimuli, the proliferation of tumour cells and to record bioelectrical activity of the system.
The multidisciplinary team is from the Free University of Bozen-Bolzano (Faculty of Science and Technology), Istituto di Struttura della Materia CNR (CNR-ISM, Rome, Italy), Cicci Research srl. (Grosseto, Italy), Eurac Research (Institute for Biomedicine, Bolzano, Italy), and Pennsylvania State University (Department of Materials Science and Engineering, Pennsylvania, USA) and coordinated by Tor Vergata University of Rome (Department of Electronic Engineering and Department of Biomedicine and Prevention).
The Department of Electronic Engineering collaborated in the creation of the bioplatform while the Department of Biomedicine and Prevention at Tor Vergata studied the cellular behavior finding a relationship between the increase in intracellular calcium, following the stimulation of light, and the slowing down of the proliferation of cancer cells.
The researchers found that light stimulation increases the concentration of calcium ions within cells by a factor of three and that, at the same time, calcium in the cells affects the non-proliferation of cells. The results of the research can open new paths towards non-invasive cell control techniques for applications in biophotonics and biomedicine and for innovative therapies in the treatment of tumours.
PHOTO-SENSITIVE BIOPLATFORM FOR THE STUDY OF CELL BEHAVIOR
We talked to the researchers about it:
«The device platform we designed - explains Prof. Thomas M. Brown, at the Electronic Engineering Department of "Tor Vergata", coordinator of the research group – enabled us to inhibit cell proliferation by 50% in a tumour cell line by subjecting the platform to a series of periodic pulses of light over time as well as to record electrical signals generated upon illumination»
«The photo-sensitive platform for cell cultures that we have designed and built allows us to study the effect of light stimuli, transduced into an electrical stimulus, on cellular activity – explains Manuela Ciocca, currently a postdoc research fellow at the Free University of Bolzano – Faculty of Science and Technology, previously PhD student at Tor Vergata's Department of Electronic Engineering, where she started the work, and first author of the article. "We have verified that the photo-transduction process mediated by the opto-electronic device makes it possible to inhibit the proliferation of a neuroblastoma cell line by 50%" – adds Ciocca.
BIOCOMPATIBLE INTERFACE AND ITS APPLICATIONS IN BIOMEDICINE
For Tor Vergata, in addition to the electronic engineers, Antonella Camaioni, associate professor of Histology, and Serena Marcozzi, postdoc research fellow, at the Department of Biomedicine and Prevention, collaborated in the research on the biological interface.
The interface of organic polymer semiconductors and biological systems is one of the newest frontiers of bioelectronics and biotechnology. “We demonstrated the biocompatibility of the platform and the increase in intracellular calcium induced by polymer-mediated photo-transduction. This is a very important parameter since calcium is involved in many cellular processes such as contraction and proliferation. The device - continues Professor Camaioni - is therefore a new starting point for new possibilities in electrophysiological measurements».
INHIBIT CELL PROLIFERATION
We asked Professor Camaioni what causes the relationship found between the level of calcium and cell proliferation.
«Calcium ions are an important intracellular messenger for our cells. In these many proteins are calcium-dependent, i.e. they perform their function only in the presence of a certain concentration of calciumions. Let us consider, for example, that the contraction of our muscles, the skeletal as well as the cardiac and smooth ones, is possible thanks to the presence of proteins that bind calcium. This is why the calcium ion is normally kept "outside" the cells or "sequestered" in closed compartments within them and recalled into the cytoplasm only "when needed", we could say "on demand".
In our experimentation - continues the medical biologist from "Tor Vergata" - the light pulse protocol applied to the cells of a human neuroblastoma tumour line determined the opening of membrane channels for calcium ions. These, upon entering the cytoplasm, went to bind to intracellular proteins, we do not yet know which ones, which led to a slowdown in cell proliferation, a very interesting phenomenon that we would like to further investigate"
FUTURE APPLICATIONS: REGENERATIVE MEDICINE AND CELL THERAPY
The results of the work may indicate new directions for the in vitro control of cellular behavior via light pulses and open new opportunities for non-invasive photostimulation, manipulation and control techniques for cells for application in biophotonics, biomedicine and innovative therapies for cancer treatments as well as biosensing.
«Recently, organic and photosensitive semiconductor materials have shown great promise, even implanted in vivo – says Brown – for the transduction of light stimuli into excitation signals for cells and tissues, including degenerated retinas. These materials are flexible and can be deposited like common inks».
The Vice President for Research of Tor Vergata University of Rome, Prof. Massimo Federici, commented that “Exciting results such as these are made possible when teams from different departments, institutions and even countries – Italy and USA in this case - come together with their multidisciplinary expertise to bring innovation and new understanding in their respective fields, i.e. electronics, biology, materials science, physics and bio-medicine in this instance.”
The research, entitled “A Polymer Bio–Photoelectrolytic Platform for Electrical Signal Measurement and for Light Modulation of Ion Fluxes and Proliferation in a Neuroblastoma Cell Line”, supported by Tor Vergata University of Rome's “Mission: Sustainability”, the Lazio Region (Torno Subito and Progetto di Gruppo di Ricerca finanziato ai sensi della L.R. Lazio 13/08 n. 85-2017-15373), The Tuscany Region (POR-FESR 2014-2020), and the United States Air Force Office of Scientific Research (FA9550-20-1-0157 and FA9550-18-1-0233 Bio Physics and Natural Materials) is published in the open access international journal Advanced NanoBioMed Research (DOI: 10.1002/anbr.202200127). Figure 1: Conjugated polymer bio–photoelectrolytic platform. Schematic of the open‐top (left) and sandwich‐closed (right) architecture.