Terahertz zaps alter gene activity in stem cells

                         

Using the apparatus, which effectively exposes iPSCs to terahertz radiation, the researchers found that terahertz light pulses change the activity of genes influenced by zinc-dependent transcription factors. Credit: Mindy Takamiya/Kyoto University iCeMS (CC BY-NC-SA 4.0)

https://phys.org/news/2020-10-terahertz-zaps-gene-stem-cells.html

Terahertz light pulses change gene expression in stem cells, report researchers from Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) and Tokai University in Japan in the journal Optics Letters. The findings come thanks to a new tool, with implications for stem cell research and regenerative therapy development.

Terahertz waves fall in the far infrared/microwave part of the electromagnetic spectrum and can be produced by powerful lasers. Scientists have used terahertz pulses to control the properties of solid-state materials. They also have potential for manipulating living cells, as they don't damage them the way that ultraviolet or infrared light does. Research so far has led to contradictory findings about their effects on cells, possibly because of the way the experiments have been conducted.

iCeMS microengineer Ken-ichiro Kamei and physicist Hideki Hirori worked with colleagues to develop a better tool for investigating what happens when terahertz pulses are shone on human cells. The apparatus overcomes issues with previous techniques by placing cells in tiny microwells that have the same area as the terahertz light.

The team used the apparatus to explore the effects of terahertz radiation on induced pluripotent stem cells (iPSCs). These are cells that have been taken from skin or blood and changed into stem cells. Scientists are seeking to turn them into other types of cells and tissues to help treat diseases like muscular dystrophy.

"Terahertz pulses can generate a strong electric field without touching or damaging cells," says Hirori. "We tested their effect on iPSCs and discovered that the activity of some gene networks changes as a result of terahertz light exposure."

For example, they found the pulses activated genes involved in motor neuron survival and mitochondrial function. They also deactivated genes involved in cell differentiation, the process in which stem cells change into specialized body cells.

Further investigation found that these genes were influenced by zinc-dependent transcription factors. The scientists believe the terahertz pulses generate an electric field that causes zinc ions to move inside cells, impacting the function of transcription factors, which in turn activate or deactivate the genes they are responsible for.

Hirori says the findings could aid efforts to develop a technology that can manipulate iPSC differentiation into specific cells by turning off specific genes while keeping others on, paving the way for regenerative therapies for a wide range of diseases.

Abstract-Detection and manipulation of methylation in blood cancer DNA using terahertz radiation

Hwayeong Cheon, Jin Ho Paik, Moran Choi, Hee-Jin Yang,  Joo-Hiuk Son

https://www.nature.com/articles/s41598-019-42855-x

DNA methylation is a pivotal epigenetic modification of DNA that regulates gene expression. Abnormal regulation of gene expression is closely related to carcinogenesis, which is why the assessment of DNA methylation is a key factor in cancer research. Terahertz radiation may play an important role in active demethylation for cancer therapy because the characteristic frequency of the methylated DNA exists in the terahertz region. Here, we present a novel technique for the detection and manipulation of DNA methylation using terahertz radiation in blood cancer cell lines. We observed the degree of DNA methylation in blood cancer at the characteristic resonance of approximately 1.7 THz using terahertz time-domain spectroscopy. The terahertz results were cross-checked with global DNA methylation quantification using an enzyme-linked immunosorbent assay. We also achieved the demethylation of cancer DNA using high-power terahertz radiation at the 1.7-THz resonance. The demethylation degrees ranged from 10% to 70%, depending on the type of cancer cell line. Our results show the detection of DNA methylation based on the terahertz molecular resonance and the manipulation of global DNA methylation using high-power terahertz radiation. Terahertz radiation may have potential applications as an epigenetic inhibitor in cancer treatment, by virtue of its ability to induce DNA demethylation, similarly to decitabine.

Abstract-Determination of tenogenic differentiation in human mesenchymal stem cells by terahertz waves for measurement of the optical property of cellular suspensions

Yasuyuki Morita, Kosuke Azuchi, Yang Ju, Satoshi Suzuki, Baiyao Xu and Shuhei Yamamoto

http://iopscience.iop.org/0957-0233/25/6/065703/article
ju@mech.nagoya-u.ac.jp

Department of Mechanical Science and Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan
 

Yasuyuki Morita et al 2014 Meas. Sci. Technol. 25 065703. doi:10.1088/0957-0233/25/6/065703
Received 18 November 2013, accepted for publication 28 March 2014. Published 12 May 2014.
© 2014 IOP Publishing Ltd

Abstract

Technology for identifying stem cell-to-tenocyte differentiation that is non-contact and non-destructive in vitro is essential in tissue engineering. It has been found that expression of various RNA and proteins produced by differentiated cells is elevated when human bone marrow mesenchymal stem cells (hBMSCs) differentiate into tenocytes. Also, such biomolecules have absorption bands in the terahertz range. Thus, we attempted to evaluate whether terahertz waves could be used to distinguish hBMSC-to-tenocyte differentiation. Terahertz time-domain spectroscopy (THz-TDS) using femtosecond laser pulses was used for terahertz measurements. HBMSCs differentiated into tenocytes with mechanical stimulation: 10% cyclical uniaxial stretching at 1 Hz for 24 or 48 h. Cellular suspensions before and after differentiation were measured with terahertz waves. Complex refractive index, consisting of a refractive index (real) and an extinction coefficient (imaginary) obtained from the transmitted terahertz signals, was evaluated before and after differentiation at 1.0 THz. As a result, the THz-TDS system enabled discrimination of hBMSC-to-tenocyte differentiation due to the marked contrast in optical parameter before and after differentiation. This is the first report of the potential of a THz-TDS system for the detection of tenogenic differentiation using a non-contact and non-destructive in vitro technique.

Abstract-Effect of intense THz pulses on expression of genes associated with skin cancer and inflammatory skin conditions

Lyubov V. Titova, Ayesheshim K. Ayesheshim, David Purschke, Frank A. Hegmann

Univ. of Alberta (Canada)

Andrey Golubov, Rocio Rodriguez-Juarez, Rafal Woycicki, Olga Kovalchuk

Univ. of Lethbridge (Canada)

Proc. SPIE 8941, Optical Interactions with Tissue and Cells XXV; and Terahertz for Biomedical Applications, 89411G (March 13, 2014); doi:10.1117/12.2044167

http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=1850014

The growing experimental evidence suggests that broadband, picosecond-duration THz pulses may influence biological systems and functions. While the mechanisms by which THz pulse-induced biological effects are not yet known, experiments using in vitro cell cultures, tissue models, as well as recent in vivo studies have demonstrated that THz pulses can elicit cellular and molecular changes in exposed cells and tissues in the absence of thermal effects. Recently, we demonstrated that intense, picosecond THz pulses induce phosphorylation of H2AX, indicative of DNA damage, and at the same time activate DNA damage response in human skin tissues. We also find that intense THz pulses have a profound impact on global gene expression in human skin. Many of the affected genes have important functions in epidermal differentiation and have been implicated in skin cancer and inflammatory skin conditions. The observed THzinduced changes in expression of these genes are in many cases opposite to disease-related changes, suggesting possible therapeutic applications of intense THz pulses. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

University of Buffalo-The symphony of life, revealed

http://www.buffalo.edu/news/releases/2014/01/012.html

Using a new imaging technique they developed, scientists have managed to observe and document the vibrations of lysozyme, an antibacterial protein found in many animals. This graphic visualizes the vibrations in lysozyme as it is excited by terahertz light (depicted by the red wave arrow). Credit: Andrea Markelz and Katherine Niessen.

A new imaging technique captures the vibrations of proteins, tiny motions critical to human life

By Charlotte Hsu

Release Date: January 16, 2014

BUFFALO, N.Y. — Like the strings on a violin or the pipes of an organ, the proteins in the human body vibrate in different patterns, scientists have long suspected.

Now, a new study provides what researchers say is the first conclusive evidence that this is true.

Using a technique they developed based on terahertz near-field microscopy, scientists from the University at Buffalo and Hauptman-Woodward Medical Research Institute (HWI) have for the first time observed in detail the vibrations of lysozyme, an antibacterial protein found in many animals.

The team found that the vibrations, which were previously thought to dissipate quickly, actually persist in molecules like the “ringing of a bell,” said UB physics professor Andrea Markelz, PhD, wh0 led the study.

These tiny motions enable proteins to change shape quickly so they can readily bind to other proteins, a process that is necessary for the body to perform critical biological functions like absorbing oxygen, repairing cells and replicating DNA, Markelz said.

The research opens the door to a whole new way of studying the basic cellular processes that enable life.

“People have been trying to measure these vibrations in proteins for many, many years, since the 1960s,” Markelz said. “In the past, to look at these large-scale, correlated motions in proteins was a challenge that required extremely dry and cold environments and expensive facilities.”

“Our technique is easier and much faster,” she said. “You don’t need to cool the proteins to below freezing or use a synchrotron light source or a nuclear reactor — all things people have used previously to try and examine these vibrations.”

The findings appear today in Nature Communications.

To observe the protein vibrations, Markelz’ team relied on an interesting characteristic of proteins: The fact that they vibrate at the same frequency as the light they absorb.

This is analogous to the way wine glasses tremble and shatter when a singer hits exactly the right note. Markelz explained: Wine glasses vibrate because they are absorbing the energy of sound waves, and the shape of a glass determines what pitches of sound it can absorb. Similarly, proteins with different structures will absorb and vibrate in response to light of different frequencies.

So, to study vibrations in lysozyme, Markelz and her colleagues exposed a sample to light of different frequencies and polarizations, and measured the types of light the protein absorbed.

This technique, developed with Edward Snell, a senior research scientist at HWI and assistant professor of structural biology at UB, allowed the team to identify which sections of the protein vibrated under normal biological conditions. The researchers were also able to see that the vibrations endured over time, challenging existing assumptions.

“If you tap on a bell, it rings for some time, and with a sound that is specific to the bell. This is how the proteins behave,” Markelz said. “Many scientists have previously thought a protein is more like a wet sponge than a bell: If you tap on a wet sponge, you don’t get any sustained sound.”

Markelz said the team’s technique for studying vibrations could be used in the future to document how natural and artificial inhibitors stop proteins from performing vital functions by blocking desired vibrations.

“We can now try to understand the actual structural mechanisms behind these biological processes and how they are controlled,” Markelz said.

“The cellular system is just amazing,” she said. “You can think of a cell as a little machine that does lots of different things — it senses, it makes more of itself, it reads and replicates DNA, and for all of these things to occur, proteins have to vibrate and interact with one another.”

Left to right: Andrea Markelz and Katherine Niessen, two of the study's University at Buffalo coauthors. Credit: Douglas Levere

Media Contact Information

Charlotte Hsu
Media Relations Manager, Architecture, Economic Development, Sciences, Urban and Regional Planning
Tel: 716-645-4655
chsu22@buffalo.edu
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Terahertz Radiation Increases Production of Proteins to Fight Cancer but also Damages DNA

http://www.medindia.net/news/terahertz-radiation-increases-production-of-proteins-to-fight-cancer-but-also-damages-dna-115920-1.htm

My note: Here is one more article on one of the most intriguing THz discoveries in recent memory.

A new study has found that Terahertz (THz) radiation, a section of electromagnetic spectrum between microwave and infrared light, may be effective in fighting cancer by increasing the production of proteins that aid the immune system in fighting the cancer cells. But the issue is that this can also lead to DNA damage.

The findings, which are the result of a collaboration between physicists at the University of Alberta and molecular biologists at the University of Lethbridge in Canada, are published today in the Optical Society's (OSA) open-access journal Biomedical Optics Express. 

"While these investigations of the biological effects of intense THz pulses are only just beginning," said Lyubov Titova, with the University of Alberta and a member of the research team, "the fact that intense THz pulses can induce DNA damage but also DNA repair mechanisms in human skin tissue suggests that intense THz pulses need to be evaluated for possible therapeutic applications." 

THz photons, like their longer wavelength cousins in the microwave range, are not energetic enough to break the chemical bonds that bind DNA together in the nucleus of cells. These waves, however, have just the right frequency to energize water molecules, causing them to vibrate and produce heat, which is why microwave ovens are so efficient at cooking food. For this reason, it was believed that heat-related injuries were the principal risks posed by THz radiation exposure. 

Recent theoretical studies, however, suggest that intense THz pulses of picosecond (one trillionth of a second) duration may directly affect DNA by amplifying natural vibrations (the so-called "breathing" mode) of the hydrogen bonds that bind together the two strands of DNA. As a result, "bubbles" or openings in DNA strands can form. According to the researchers, this raised the question: "Can intense THz pulses destabilize DNA structure enough to cause DNA strand breaks?" 

As shown in earlier animal cell culture studies, THz exposure may indeed affect biological function under specific conditions such as high power and extended exposure. There is, however, a vast gulf between animal research and conclusions that can be drawn about human health. 

In a first of its kind study, the Canadian researchers exposed laboratory-grown human skin tissue to intense pulses of THz electromagnetic radiation and have detected the telltale signs of DNA damage through a chemical marker known as phosphorylated H2AX. At the same time, they observed THz-pulse induced increases in the levels of multiple tumor suppressor and cell-cycle regulatory proteins that facilitate DNA repair. This may suggest that DNA damage in human skin arising from intense picosecond THz pulse exposure could be quickly and efficiently repaired, therefore minimizing the risk of carcinogenesis. 

Source-Eurekalert

Read more: Terahertz Radiation Increases Production of Proteins to Fight Cancer but also Damages DNA | Medindia http://www.medindia.net/news/terahertz-radiation-increases-production-of-proteins-to-fight-cancer-but-also-damages-dna-115920-1.htm#ixzz2O9g7H4Lm

Intense Terahertz Pulses Cause DNA Damage But Also Induce DNA Repair

http://www.businesswire.com/news/leaderpost/20130314005729/en/Intense-Terahertz-Pulses-DNA-Damage-Induce-DNA

Biomedical Optics Express research details how terahertz pulses that destroy skin tissue at the same time increase tumor-suppressing proteins

WASHINGTON--(BUSINESS WIRE)--Terahertz (THz) radiation, a slice of the electromagnetic spectrum that occupies the middle ground between microwaves and infrared light, is rapidly finding important uses in medical diagnostics, security, and scientific research. As scientists and engineers find evermore practical uses for this form of radiation, questions persist about its potential human health risks.

“In the future, we plan to study how all the observed effects change with time after exposure, which should allow us to establish how quickly any induced damage is repaired.”

New research performed on lab-grown human skin suggests that short but powerful bursts of THz radiation may both cause DNA damage and increase the production of proteins that help the body fight cancer. The findings, which are the result of a collaboration between physicists at the University of Alberta and molecular biologists at the University of Lethbridge in Canada, are published today in the Optical Society’s (OSA) open-access journalBiomedical Optics Express.

“While these investigations of the biological effects of intense THz pulses are only just beginning,” said Lyubov Titova, with the University of Alberta and a member of the research team, “the fact that intense THz pulses can induce DNA damage but also DNA repair mechanisms in human skin tissue suggests that intense THz pulses need to be evaluated for possible therapeutic applications.”

THz photons, like their longer wavelength cousins in the microwave range, are not energetic enough to break the chemical bonds that bind DNA together in the nucleus of cells. These waves, however, have just the right frequency to energize water molecules, causing them to vibrate and produce heat, which is why microwave ovens are so efficient at cooking food. For this reason, it was believed that heat-related injuries were the principal risks posed by THz radiation exposure.

Recent theoretical studies, however, suggest that intense THz pulses of picosecond (one trillionth of a second) duration may directly affect DNA by amplifying natural vibrations (the so-called “breathing” mode) of the hydrogen bonds that bind together the two strands of DNA. As a result, “bubbles” or openings in DNA strands can form. According to the researchers, this raised the question: “Can intense THz pulses destabilize DNA structure enough to cause DNA strand breaks?”

As shown in earlier animal cell culture studies, THz exposure may indeed affect biological function under specific conditions such as high power and extended exposure. There is, however, a vast gulf between animal research and conclusions that can be drawn about human health.

In a first of its kind study, the Canadian researchers exposed laboratory-grown human skin tissue to intense pulses of THz electromagnetic radiation and have detected the telltale signs of DNA damage through a chemical marker known as phosphorylated H2AX. At the same time, they observed THz-pulse induced increases in the levels of multiple tumor suppressor and cell-cycle regulatory proteins that facilitate DNA repair. This may suggest that DNA damage in human skin arising from intense picosecond THz pulse exposure could be quickly and efficiently repaired, therefore minimizing the risk of carcinogenesis.

The researchers used a skin tissue model made of normal, human-derived epidermal and dermal cells. This tissue is able to undergo mitosis (cell division) and is metabolically active, thus providing an appropriate platform for assessing the effects of exposure to high intensity THz pulses on human skin. For their study, Titova and her colleagues exposed the skin tissue to picosecond bursts of THz radiation at levels far above what would typically be used in current real-world applications. They then studied the sample for the presence of phosphorylated H2AX, which “flags” the DNA double strand break site and attracts cellular DNA repair machinery to it.

“The increase in the amount of phosphorylated H2AX in tissues exposed to intense THz pulses compared to unexposed controls indicated that DNA double strand breaks were indeed induced by intense THz pulses,” observed Titova. Once DNA breaks occur, they can eventually lead to tumors if unrepaired. “This process,” she continued, “is very slow and cells have evolved many effective mechanisms to recognize damage, pause cell cycle to allow time for damage to be repaired, and – in case repair is unsuccessful – to prevent damage accumulation by inducing apoptosis, or programmed cell death of the affected cell.”

The researchers confirmed that these cellular repair mechanisms were taking place by detecting an elevated presence of multiple proteins that play vital roles in DNA repair, including protein p53 (often called “a guardian of the genome”); p21, which works to stop cell division to allow time for repair; protein Ku70, which helps reconnect the broken DNA strands; and several other important cell proteins with known tumor-suppressor roles. These observations indicate that exposure to intense THz pulses activates cellular mechanisms that repair DNA damage. However, the researchers note, it is too soon to make predictions on the long-term implications of exposure.

“In our study we only looked at one moment in time – 30 minutes after exposure,” Titova said. “In the future, we plan to study how all the observed effects change with time after exposure, which should allow us to establish how quickly any induced damage is repaired.”

The Canadian researchers hope to explore the potential therapeutic effects of intense THz radiation exposure to see if directed treatment with intense THz pulses can become a new tool to fight cancer.

Paper: “Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin in vivo,” Titova, L. V. et al., Biomedical Optics Express, Vol. 4, Issue 4, pp. 559-568 (2013).

EDITOR’S NOTE: High-resolution images are available to members of the media upon request. Contact Angela Stark, astark@osa.org

About Biomedical Optics Express

Biomedical Optics Express is OSA’s principal outlet for serving the biomedical optics community with rapid, open-access, peer-reviewed papers related to optics, photonics and imaging in the life sciences. The journal scope encompasses theoretical modeling and simulations, technology development, and biomedical studies and clinical applications. It is published by the Optical Society and edited by Joseph A. Izatt of Duke University. Biomedical Optics Express is an open-access journal and is available at no cost to readers online at www.OpticsInfoBase.org/BOE.

About OSA

Uniting more than 180,000 professionals from 175 countries, the Optical Society (OSA) brings together the global optics community through its programs and initiatives. Since 1916 OSA has worked to advance the common interests of the field, providing educational resources to the scientists, engineers and business leaders who work in the field by promoting the science of light and the advanced technologies made possible by optics and photonics. OSA publications, events, technical groups and programs foster optics knowledge and scientific collaboration among all those with an interest in optics and photonics. For more information, visit www.osa.org.

Contacts

The Optical Society
Angela Stark, 202-416-1443
astark@osa.org

Wound response in fs-THz-irradiated mouse skin

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44671
Title:Wound response in fs-THz-irradiated mouse skin 
 Organism: Mus musculus
 Experiment type: Expression profiling by array

Summary: Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NFκB1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-β). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF-β and activation of its downstream target genes, which perturbs the wound healing process in vivo.

Overall design: To identify non-thermally induced in vivo mode action of THz radiation, gene expression profile of fs-THz-irradiated skin (at post 24-hours after 1 hour exposure) was explored. Purified total RNAs from independent 3 mice of each sham and THz group were labeled and hybridized on the Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA), according to manufacturer's standard protocol. Statistically filtered THz-responsive genes were examined for possible interactions with other molecules, canonical signaling pathways, and bio-functions.
Contributor(s) Kim K, Park J, Jo S, Jung S, Park G, Kwon O, Park W

DoD basic research discovers new spectroscopic signatures from the "stuff of life"

Physics professor Elliott Brown and graduate student Anna Lukawska work in the lab on nanobiological characterizations.

http://phys.org/news/2012-05-dod-basic-spectroscopic-signatures-life.html

Naturally, DNA sensing and identification has become a very important technology in such areas as biology, medicine and law enforcement. But positive identification without ambiguity is difficult because DNA is so sparse in the human organism and because it shares many of the same chemical bonds as other more common biomolecules–proteins and polysaccharides.

So traditional spectroscopic methods, such as infrared transmission, cannot distinguish DNA from these other molecules. More elaborate techniques are necessary, such as polymerase chain reaction (PCR) followed by gel electrophoresis, which are expensive and time-consuming.

Fortunately, the large size of DNA molecules makes them amenable to other spectroscopic methods in the THz region of the electromagnetic spectrum–a region well below the infrared in frequency but well above common radio and radar frequencies.

Wright State University researchers led by physics professor Elliott Brown have been investigating these unique THz DNA signatures through a Multidisciplinary University Research Initiative (MURI) funded by the U.S. Army Research Office. Their multi-year $600,000 grant has recently identified several unique and surprisingly strong signatures from DNA molecules between 0.7 and 1.0 THz.

“The surprise is that we have recently measured these DNA signatures under physiological conditions in which the DNA was suspended in an aqueous buffer solution very similar to that in living cells,” Brown said. “Previously, the strong THz absorption by liquid water was thought to be too strong to observe signatures from any suspended molecular species.”

So far, Brown said, the signatures appear unique to the DNA molecule at hand, be it single-stranded or double-stranded DNA.

“The caveat is that so far we have only observed relatively short DNA strands well under the length of the human genome,” he said. “But we are moving in that direction.”

The research project is headed by the University of California-Irvine, and along with Wright State University has collaborators at Marshall University, Yale University and the University of Chicago. The MURI Grant funds the research for up to five years.