Terahertz pulse-altered gene networks in human induced pluripotent stem cells via Zinc signal

Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes.

THz-regulated genes were driven by zinc–finger transcription factors. Combined with a consideration of the interactions of metal ions and a THz electric field, these results imply that the local intracellular concentration of metal ions, such as Zn2+, was changed by the effective electrical force of the THz pulse.

THz pulse excitation has excellent potential to manipulate living cells in a non-invasive manner, because it drives the intra- and intermolecular vibrational modes of biological molecules, such as DNA, RNA, or proteins without physically disrupting the cell membrane.

These effects are believed to cause changes in intracellular ions, such as metal ions and pH, gene expression, protein folding, biomolecule interactions, electron transfer, and enzymatic activity.

THz irradiation modulated cytoskeleton arrangement to facilitate adhesion for hiPSCs.

In particular, Zn2+ plays an important role in regulating the activity of transcription factors and in controlling gene expression. ZNFs are known to be the most abundant protein superfamily in the mammalian genome. The THz electric field allows the acceleration of electrical charges, including those of free electrons in vacuum and metal ions, by providing a large ponderomotive energy (kinetic energy of a charged particle in an oscillating electric field). This suggests a model in which THz pulses drive metal ions in a cell to alter gene expression.

Gene expression was induced nonthermally by the electric field of the THz pulse.

The genes that were strongly affected by THz irradiation were identified to be regulated ZNFs. This suggests that the unipolar THz pulse causes movement of Zn2+. ZNFs are one of the most abundant proteins and play important roles in a range of cellular functions, including physiological and pathological conditions.

Functionally, modulation of Nanog expression by Zfp281 is an efficient mechanism to fine-tune reprogramming activity.

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