Researchers at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, have now unveiled a remarkable discovery that allows for the controlled activation of proteins through the power of heat.
Controlling Cell Death with Heat: The Future of Thermogenetics
The research team at Kanazawa University’s Nano Life Science Institute (WPI-NanoLSI) recently created a new thermogenetic tool using special biological materials called elastin-like polypeptides (ELPs). These proteins respond to mild heating by changing their structure, which then activates another protein known as caspase-8 (CASP8). Caspase-8 plays a key role in starting programmed cell death, or apoptosis, which is crucial for healthy body development and fighting diseases.
Thermogenetics is an exciting branch of science that uses heat to control the activity of proteins inside living cells. This type of precise control helps scientists understand and influence how cells behave, which is important for developing new treatments for diseases. Unlike optogenetics, which uses light but struggles to work deep inside tissues, thermogenetics can activate cells even in hard-to-reach areas by using localized heating methods such as infrared lasers or focused ultrasound. This ability provides a powerful tool for research in medicine and biology, especially when very exact timing and location are needed to switch proteins on or off inside single cells.
Different Ways Scientists Control Proteins
Here’s how scientists currently manipulate proteins:
- Chemogenetics: Uses chemical agents to induce protein interactions but lacks quick reversibility.
- Optogenetics: Employs light-sensitive proteins to offer rapid control but faces limits due to light penetration issues in body tissues.
- Thermogenetics: Controls cell functions by changing temperature and works well where light does not penetrate effectively.
The Role of Elastin-Like Polypeptides (ELPs) in Heat Activation
A recent breakthrough involves using special molecules called elastin-like polypeptides (ELPs). These molecules change their shape when heated past a certain temperature called the phase transition temperature (Tt). Below this temperature, ELPs stay dissolved in water. But above it, they clump together, creating an opportunity to bring attached proteins close enough that they become activated.
The Design of Heat-Activated Human CASP8 Protein
The team fused ELPs with the human enzyme caspase 8 (CASP8). CASP8 plays a key role in kicking off apoptosis—programmed cell death—which is a natural process that removes damaged or unneeded cells. When the fused protein experiences heat above its Tt, ELPs cause CASP8 molecules to gather tightly. This gathering boosts CASP8 activation by encouraging dimerization and autocleavage—triggering the cell’s self-destruction pathway. Thus, heat acts like a precise switch controlling when cell death begins.
Mild Heating for Safe Activation
The researchers designed the system so it activates at temperatures only slightly higher than normal body temperature (~37 °C). This mild heating makes it possible to trigger specific responses without damaging surrounding tissues. It also allows highly precise control by focusing infrared lasers on targeted single cells in real time. Such specificity could lead to novel treatments where only disease-causing cells are eliminated while healthy ones remain unharmed.
How They Proved Their Thermogenetic System Works
To confirm their system’s effectiveness, researchers added a fluorescent indicator to detect caspase-8 activation visually. This involved special glowing proteins that move into the cell’s nucleus when caspase-8 switches on, allowing easy measurement under a microscope.
Testing on Human Cells
The team applied their thermogenetic tool to human kidney-derived cells. Upon raising the temperature slightly above normal body temperature, they observed that controlled activation of caspase-8 led to programmed cell death. This proves that their heat-based system functions safely at mild temperatures without damaging other parts of the cell.
The Impact on Future Science and Medicine
This thermogenetic approach overcomes many problems seen with previous techniques, like slow response times or the inability to target deep tissues accurately. Thanks to ELPs’ unique properties and advanced heating tools, scientists can now more effectively study how programmed cell death operates at the single-cell level. This understanding may lead to breakthroughs in cancer therapy, neurodegenerative diseases, and tissue engineering.
Reference
- Vu, C. Q., & Arai, S. (2025). A thermogenetic tool employing elastin-like polypeptides for controlling programmed cell death. ACS Nano. https://doi.org/10.1021/acsnano.5c07332
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Neha Adikane holds a Master’s degree in Environmental Science from Pune University, bringing a unique blend of scientific expertise and creative writing skills to her craft. She specializes in creating engaging, insightful, and impactful content across various niches. With a passion for translating complex ideas into simple, relatable narratives, she excels at crafting blogs, articles, website content, and social media posts that captivate readers and drive engagement. Neha’s background in environmental science adds depth to her writing, allowing her to effectively cover topics related to sustainability, eco-awareness, and scientific innovations.
