5G technology: bridging in vitro and in silico models to investigate the interaction mechanisms at cellular level: 5G:SMILE

PRIN 2022 Maffei

Abstract

5G technology: bridging in vitro and in silico models to investigate the interaction mechanisms at cellular level: 5G:SMILE PRIN 2022 Aicardi – Maffei Abstract: The deployment of 5G mobile networks is significantly increasing wireless devices and transmitting antennas. This technology also employs frequencies in the millimeter wave (mmW) range, in the FR2 band (26–29 GHz). Although sporadic adverse health effect has been causally linked to exposure to wireless technologies, the knowledge on possible effects of 5G signal exposure in the mmW range at cellular level is certainly insufficient at the moment. The aim of this project is to provide evidence for a possible cellular mechanism underneath the interaction between the 26.5 GHz 5G-modulated signal and biological systems. The project combined in vitro experiments on human keratinocytes with advanced in silico approaches, including electromagnetic and dosimetric modelling, microdosimetry, and atomistic molecular dynamics simulations. Bringing together expertise in engineering, physics, biology, and bioelectromagnetics, the project aimed to develop standardized exposure protocols, implement innovative and well-characterized exposure systems, evaluate cellular responses under controlled conditions, and identify potential molecular mechanisms underlying electromagnetic field interactions. A major achievement of the project was the development of novel exposure platforms enabling both conventional and real-time live-cell experiments under confocal microscopy, ensuring accurate dosimetric characterization and high experimental reproducibility. These experimental activities were complemented by realistic three-dimensional cellular models and molecular simulations of biologically relevant proteins, providing a mechanistic framework for interpreting the experimental observations.

Results achieved

: The project successfully achieved nearly all of its planned objectives, delivering innovative experimental platforms and standardized methodologies for investigating the biological effects of millimeter-wave 5G signals. Newly developed exposure systems enable controlled irradiation of cell cultures as well as real-time imaging experiments, representing a significant technological advancement for bioelectromagnetic research. Experimental studies on human keratinocytes showed that exposure to a 26.5 GHz 5G-modulated signal induced transient cellular responses, including a temporary increase in reactive oxygen species (ROS) production and changes in mitochondrial membrane potential. No significant changes were observed in superoxide dismutase (SOD) activity under the investigated exposure conditions, suggesting adaptive rather than persistent biological responses. Genome-wide DNA methylation analyses in cells exposed to the 5G signal are underway. Experimental protocols for investigating the effect of 5G exposure on TRPV4 ion channel activity and intracellular calcium dynamics were successfully established; exposure experiments using the newly developed real-time systems will be completed soon. On the computational side, realistic three-dimensional models of human keratinocytes enabled high-resolution microdosimetric analyses, demonstrating how local electromagnetic field distributions are influenced by cellular morphology and tissue organization. Molecular dynamics simulations of biologically relevant targets - including the TRPV4 ion channel SOD, and NADPH oxidase 5 (NOX5) - showed that, at the investigated frequencies, electromagnetic fields primarily affect water polarization dynamics and selected molecular processes without inducing significant structural changes in the proteins. These findings provide a mechanistic interpretation consistent with the experimental observations. Beyond the specific biological findings, the project produced a comprehensive research infrastructure comprising validated exposure systems, advanced dosimetric tools, realistic three-dimensional cellular models, and molecular simulation workflows that can be applied to future investigations on emerging wireless technologies. The interdisciplinary integration of engineering, computational modelling and experimental biology has generated a coherent mechanistic framework that strengthens the interpretation of experimental observations and represents a valuable resource for the international bioelectromagnetics community. The project has already resulted in a peer-reviewed publication, numerous presentations at major international conferences, and the establishment of new scientific collaborations, thereby reinforcing Italy's contribution to research on the biological effects of radiofrequency electromagnetic fields. Overall, 5G:SMILE has delivered innovative experimental and computational tools for investigating the biological effects of 5G millimeter-wave exposure and has generated new scientific evidence contributing to the understanding of electromagnetic field interactions with biological systems. These results provide a solid foundation for future research aimed at supporting evidence-based assessments of the safety and biomedical implications of next-generation wireless technologies. Responsabile scientifico:Giorgio Aicardi (28/09/2023 – 31/10/2025); Francesca Maffei (01/11/2025 – 28/02/2026) Strutture Unibo coinvolte: Dipartimento di Scienze per la Qualità della Vita Coordinatore CNR - Consiglio Nazionale delle Ricerche (Italy) (28/09/2023 - 31/03/2024); Sapienza Università di Roma (Italy) (01/04/2024 - 28/02/2026) Contributo totale Unibo: Euro (EUR) 50.118,00 Durata del progetto in mesi: 24 + 5

Dettagli del progetto

Responsabile scientifico: Francesca Maffei

Strutture Unibo coinvolte:
Dipartimento di Scienze per la Qualità della Vita

Coordinatore:
CNR - Consiglio Nazionale delle Ricerche(Italy)

Contributo totale Unibo: Euro (EUR) 50.118,00
Durata del progetto in mesi: 24
Data di inizio 28/09/2023
Data di fine: 28/02/2026

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