Computational And Experimental Study Of The Impact Of Plasma On The Human Epidermal Growth Factor And Its Implications For Wound Healing And Cancer Treatment

Abstract

The human epidermal growth factor (hEGF) plays an important role in wound healing as well as in cancer treatment. It is known to trigger chemotaxis, mitogenesis, motogenesis, and cytoprotection, allowing the promotion of cancer growth [1]. On the other hand, exactly these triggers are beneficial for wound healing [2]. Previous studies have shown that cold atmospheric pressure plasma (CAP) treatment of proteins can lead to oxidation, causing structural and conformational changes [3]. In this study, we perform computer simulations and experiments to investigate the impact of plasma treatment on hEGF. Conformational changes with different degrees of oxidation, corresponding to short or longer CAP treatment times, are studied by combining simulation results with Fourier transform infrared spectroscopy. Additional experiments are performed with circular dichroism spectroscopy to verify the simulated conformational changes. The results, being qualitatively in good agreement, indicate a more flexible structure after oxidization, due to conformational changes and breakage of disulfide bonds. Docking simulations reveal that a low oxidation degree does not have a significant influence on the binding affinity of hEGF to its receptor. However, a highly oxidized hEGF exhibits less interaction, probably ultimately affecting cell proliferation by either assisting or inhibiting the process. The results indicate that a low amount of oxidation, comparable to the medical CAP treatment times used for wound healing, does not cause significant changes of the structure of the hEGF protein and thus has only little impact on the interaction of hEGF with its receptor. A significant effect on the structural conformation of hEGF and the binding energy with EGFR can be achieved by higher oxidation degrees, which might ultimately lead to inhibition of cell growth or proliferation. This might be important in cancer treatment by means of CAP, as higher doses of oxidation arrest the cell growth, leading to apoptosis or even necrosis [4,5,6].