Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT)

Aim: Heating by nanoparticles, which are located in the tissue to be treated, is a well-recognized method in hyperthermic oncology. Our objective is to investigate selective, nanoscopic heating without concentrating extra artificial nanoparticles. We have in silico calculation to study the heating of the transmembrane protein clusters (rafts) on cell-membrane. The transmembrane protein domains have significantly higher dielectric constant than their lipid neighborhood in the membrane. This difference causes a local gradient in the Specific Absorption Rate (SAR), which could be a factor of heating of the membranes locally, as well as exciting the receptors for various signal transduction in the cells. We suppose that this process determines the observed cellular effects of modulated electro-hyperthermia (mEHT, trade-name: oncothermia). Materials and Methods: In silico models with highly specialized software (Computer Simulation Technology (CST), Darmstadt, Germany) were performed visualizing the selectivity for the membrane domains. Local raft models were created to simulate the electromagnetic (EM) effect of a 13.56 MHz excitation between two perfect electrical conductor plates, simulating the equipotential conditions of the sides of the membrane in the vicinity of the raft. The simulations were performed with near-field (EQS) solver of CST. The electric field, current density, and electric loss density were monitored by the simulations. The applied material properties and parameters refer to the recent literature. Results: In silico models show ten times higher energy-absorption of the transmembrane domains than that of its lipid-membrane surrounding, and intra- and extracellular neighborhood. Depending on the size, orientation, and location of the membrane rafts, the value of SAR varies, but we use only two simplified models to see the absorption properties. Taking into account the characteristics of the EM field effects we showed that the selective energy-absorption increased further by the cell-cell interactions. The model-calculation could confirm the opportunity of the local membrane heating. Conclusion: Our results indicate the heating in nanoscopic range with energy-absorption by the transmembrane proteins. The heated protein-clusters (membrane rafts) are used the same way as the artificial nanoparticles, while these absorbers are natural parts of the biological system.