交变电场作用下癌细胞和正常细胞内熵产生的测量和比较
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摘要
近年来,电场作用下细胞(特别是癌细胞)的生物学效应和外加电场的参数选择正在成为人们研究的热点。尽管这些研究非常的细致,但是忽略了癌细胞和正常细胞之间存在着巨大的热力学差别。细胞作为一个热力学系统,熵产生是必不可免的。癌细胞和正常细胞结构上存在着巨大的差异,通过理论计算可知在没有外场的作用下,癌细胞内部的熵产生明显高于正常细胞,两者之间的差值大约在2.7×10-16J/(K·s)～2.2×10-14J/(K·s)的范围内。熵流的方向是从癌细胞到正常细胞。但是在一定外场的作用下,正常细胞内部的熵产生高于癌细胞,可能阻止甚至改变熵流的方向。熵流伴随着信息流。这就可能提供了-种治疗癌症的方法。对交变电场作用下细胞内部的熵产生进行理论研究发现细胞内部的熵产生随电场强度的增加单调上升,电场强度在5-40V/cm范围内可能达到治疗要求。由此可见,在实验上研究细胞内部的熵产生是非常重要的。但是由于细胞体积小并且在培养基中,实验上测量细胞内部的熵产生是非常困难的。
本文利用细胞在电场和环境中温度变化以及此过程中细胞的热量变化,提出一种新的测量细胞熵产生的方法,设计了测量交变电场作用下细胞内部熵产生的实验装置。为了消除不确定因素,实验时间选为300s,并且使用的温度传感器可以满足测量要求,重复实验每次都使用新的细胞,时间上尽量选为连续的两天。
测量和比较了交变电场作用下两对来自人同一组织的癌细胞(MDA-MB-231人乳腺癌细胞和SMMC-7721人肝癌细胞)和正常细胞(MCF10A人乳腺上皮正常细胞和HL-7702人肝正常细胞)的熵产生。结果表明：这种方法能够非常有效的测量交变电场作用下细胞内部的熵产生。电场强度在5-40V/cm的范围内交变电场引起的癌细胞内部熵产生随着场强的增加单调上升,而正常细胞内部的熵产生是非单调上升的,电场强度在在5-30V/cm的范围内出现了一个峰值。电场强度在在5-25V/cm的范围内,电场引起的癌细胞内部熵产生和正常细胞的比值(MDA-MB-231/MCF10A和SMMC-7721/HL-7702)明显小于1。这对理论估算提供了一定的实验支持,并为进一步研究两类细胞的热力学差别提供依据。
对实验数据进行了误差分析,单因素方差分析。结果表明：误差远小于实验数据,无电场作用和电场作用下细胞具有明显的统计意义。实验过程中环境温度变化大约为0.8%,在熵产生计算中完全可以忽略。
我们提供了一个实验上研究细胞热力学性质非常有效的手段,并且可以进一步研究交变电场作用下正常细胞和癌细胞的差异。从实验结果来看,电场强度在5-25V/cm的范围内,交变电场作用下,正常细胞内部的熵产生要高于癌细胞内部的熵产生,并且癌细胞和正常细胞内部交变电场引起的熵产生差值达到了10-14J/(k·s),这已经达到了无外场时癌细胞和正常细胞内部熵产生的差值,这有可能阻止甚至反转癌细胞和正常细胞之间熵流和信息流方向的要求,从而达到治疗的要求,这将为治疗癌症提供了一个新的线索和依据。
本工作的创新之处包括：提出了一个实验上测量活细胞内部熵产生的方法；测量和比较了交变电场作用下两对来自同一组织的癌细胞和正常细胞内部的熵产生；这将提供了一个实验上研究细胞热力学性质非常有效的手段。
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.
本文利用细胞在电场和环境中温度变化以及此过程中细胞的热量变化,提出一种新的测量细胞熵产生的方法,设计了测量交变电场作用下细胞内部熵产生的实验装置。为了消除不确定因素,实验时间选为300s,并且使用的温度传感器可以满足测量要求,重复实验每次都使用新的细胞,时间上尽量选为连续的两天。
测量和比较了交变电场作用下两对来自人同一组织的癌细胞(MDA-MB-231人乳腺癌细胞和SMMC-7721人肝癌细胞)和正常细胞(MCF10A人乳腺上皮正常细胞和HL-7702人肝正常细胞)的熵产生。结果表明：这种方法能够非常有效的测量交变电场作用下细胞内部的熵产生。电场强度在5-40V/cm的范围内交变电场引起的癌细胞内部熵产生随着场强的增加单调上升,而正常细胞内部的熵产生是非单调上升的,电场强度在在5-30V/cm的范围内出现了一个峰值。电场强度在在5-25V/cm的范围内,电场引起的癌细胞内部熵产生和正常细胞的比值(MDA-MB-231/MCF10A和SMMC-7721/HL-7702)明显小于1。这对理论估算提供了一定的实验支持,并为进一步研究两类细胞的热力学差别提供依据。
对实验数据进行了误差分析,单因素方差分析。结果表明：误差远小于实验数据,无电场作用和电场作用下细胞具有明显的统计意义。实验过程中环境温度变化大约为0.8%,在熵产生计算中完全可以忽略。
我们提供了一个实验上研究细胞热力学性质非常有效的手段,并且可以进一步研究交变电场作用下正常细胞和癌细胞的差异。从实验结果来看,电场强度在5-25V/cm的范围内,交变电场作用下,正常细胞内部的熵产生要高于癌细胞内部的熵产生,并且癌细胞和正常细胞内部交变电场引起的熵产生差值达到了10-14J/(k·s),这已经达到了无外场时癌细胞和正常细胞内部熵产生的差值,这有可能阻止甚至反转癌细胞和正常细胞之间熵流和信息流方向的要求,从而达到治疗的要求,这将为治疗癌症提供了一个新的线索和依据。
本工作的创新之处包括：提出了一个实验上测量活细胞内部熵产生的方法；测量和比较了交变电场作用下两对来自同一组织的癌细胞和正常细胞内部的熵产生；这将提供了一个实验上研究细胞热力学性质非常有效的手段。
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.
引文
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