Millimeter-wave directed energy-mediated neural cell injury: insights into protein degradation and cell injury mechanisms

Background: Millimeter-wave directed energy (mmWave DE) is increasingly used in telecommunications and military applications, yet its biological effects on neuronal systems remain unclear. To characterize the spatially dependent cellular and molecular impacts of 34.14 GHz mmWave DE exposure on mouse neuroblastoma (N2A) cells as a model system. Methods: N2A cells were exposed to mmWave DE for 48 hours, generating three defined zones: Center (direct exposure), Penumbra (peripheral exposure), and Control. Morphological changes were evaluated by microscopy; viability and membrane integrity were assessed via MTT and LDH assays. Cytoskeletal protein degradation (αII-Spectrin, Vimentin) was measured by Western blot. Label-free LC-MS/MS proteomics, Gene Ontology (GO), Ingenuity Pathway Analysis (IPA), and Pathway Studio were used to define global molecular responses. Results: < 0.0001), and elevated LDH release, consistent with necrosis. Western blot revealed increased proteolysis of αII-Spectrin and Vimentin. Proteomic profiling identified >180 dysregulated proteins in the Center and 34 in the Penumbra, affecting cytoskeleton organization, mitochondrial function, and RNA processing. GO and IPA indicated activation of apoptosis, ER stress, and necrosis pathways, with inhibition of translation and cell movement. Pathway mapping linked DE-altered proteins to neurodegenerative and injury-relevant processes. Conclusion: mmWave DE exposure induces graded cellular injury, ranging from stress adaptation in peripheral regions to proteostasis collapse and structural failure in direct-hit zones. These findings support reconsideration of mmWave safety standards and highlight parallels with neurodegenerative mechanisms.