The Measurement And Comparison Of Entropy Production In Cancerous And Healthy Cells Under Alternating Electric Field

In recent years, many studies were carried out on the biological effects of cells (particularly for the cancerous cells) under electric field, and some works paid close attention to the parameter choice of electric field. Although these studies are detailed and elaborated, the huge thermodynamic difference inherent between the cancerous and the normal cells seems not to be noticed. As a thermodynamic system, the entropy production in the human organism is inevitable. There are many obvious differences between cancerous and healthy cells. It was demonstrated that the entropy production of cancer cells is always higher than that of normal cells if no external field is applied, and estimated that the range of entropy production rate is between2.7×10-16J/(K·s) and2.2×10-14J/(K·s) for normal cells. However, when external energy is input, the rate of entropy production of normal cells may exceed that of cancerous cells. The entropy current is the carrier of information current. It was proposed that the reversal of entropy flow between two kinds of cells may provide a therapeutic approach to cancer. The theoretically study showed that the entropy production in cells monotonically increases with electric field strength at5-40V/cm and may be applied to the cancer therapy. Therefore, the experimental study of entropy production in the human organism is of great significance, particularly in terms of the potential development of novel therapeutic anticancer modalities. However, the entropy production is difficult to measure in a living cell since the volume of cell is small, and it exists in the culture medium.In this paper, we put forward a new method that measures the entropy production in cells. It involves heating the sample by alternating electric field and recording the heat flow either into or from the specimen. We designed the experimental setup for measuring entropy production in cells. To eliminate the negative factors, the measurement time was chosen as300s. The temperature transducer we used can measure the temperature variation of cells and culture medium within this time duration. A fresh batch of cells was used for each repeated experiment to avoid differences in viability of the cells by prolonged treatment. The repeated experiments at the same electric field strength were performed during two consecutive days to avoid the larger change of ambient temperature.As model systems, two normal cell lines, MCF10A and HL-7702, and corresponding two cancerous cell lines, MDA-MB-231and SMMC-7721, were measured, respectively, and compared. The results show that the method is effective for entropy measurement of living organism. The scaled electroinduced entropy production rate (SEEP) of cancer cells monotonically increases with electric field strength at5-40V/cm, while that of normal cells changes nonmonotonically with electric field strength, reaching a peak at5-30V/cm. For all cell lines, the cancerous-to-normal ratio of field-induced entropy production is obviously smaller than1in a large range of field strength from5to25V/cm. It gives direct experimental support to above theoretical estimates and provides a basis for further study the thermodynamics difference between cancer and normal cells.We carried out the error and statistical analysis for experimental data. The results show that the error is much smaller and therefore all differences in temperature variation between cells under alternating electric field and those without electric field exposure are statistically significant. The change of the room temperature is about0.8%during the experimental process and it can be ignored in the calculation of entropy production.This work presents a facile and effective strategy for experimentally investigating the thermodynamic properties of the cell and gives deeper insight into the physical difference between normal and cancerous cells under electric field exposure. As the5-25V/cm alternating electric field is applied to both breast and hepatic cell lines, the field-induced entropy production rate for normal cells exceeds that of cancerous cells by about10-14J/(K·s), which is on the order of the total entropy production of a cell without applied field. As a result, the direction of the entropy flow may be reversed between cancerous and normal cells under electric field exposure, providing a novel avenue for the development of anticancer therapies.The unique aspects of our work include:(i) we proposed a novel method for the measurement of entropy production of living cells,(ⅱ) we measured and compared the entropy production of two sets of cancer and normal cells from the same tissue under the electric field exposure condition,(ⅲ) we present a facile and effective strategy for experimentally investigating the thermodynamic properties of the cell.