Carbon nanotube-assisted optical activation of TGF-β signalling by near-infrared light
Liang Lin1, Ling Liu1, Bing Zhao2
1Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Abstract:
Receptor-mediated signal transduction modulates complex cellular behaviours such as cell growth, migration and differentiation. Although photoactivatable proteins have emerged as a powerful tool for controlling molecular interactions and signalling cascades at precise times and spaces using light, many of these light-sensitive proteins are activated by ultraviolent or visible light, which has limited tissue penetration. Here, we report a single-walled carbon nanotube (SWCNT)-assisted approach that enables near-infrared light-triggered activation of transforming growth factor β (TGF-β) signal transduction, an important signalling pathway in embryonic development and cancer progression. The protein complex of TGF-β and its latency-associated peptide is conjugated onto SWCNTs, where TGF-β is inactive. Upon near-infrared irradiation, TGF-β is released through the photothermal effect of SWCNTs and becomes active. The released TGF-β activates downstream signal transduction in live cells and modulates cellular behaviours. Furthermore, preliminary studies show that the method can be used to mediate TGF-β signalling in living mice.
Insights
Researchers developed a near-infrared light-activated system using single-walled carbon nanotubes (SWCNTs) to control transforming growth factor beta (TGF-β) signaling. This method releases active TGF-β for cellular modulation and shows potential in living mice.
Area of Science:
- Biotechnology
- Biomedical Engineering
- Molecular Biology
Background:
- Receptor-mediated signal transduction regulates critical cellular functions like growth, migration, and differentiation.
- Photoactivatable proteins offer spatiotemporal control over molecular signaling but often require UV or visible light, limiting tissue penetration.
- Transforming growth factor beta (TGF-β) signaling is crucial in embryonic development and cancer progression.
Purpose of the Study:
- To develop a novel method for near-infrared light-triggered activation of TGF-β signal transduction.
- To overcome the limitations of UV/visible light activation in biological systems.
- To investigate the application of this technology in modulating cellular behavior and in vivo signaling.
Main Methods:
- Conjugation of the TGF-β/latency-associated peptide complex onto single-walled carbon nanotubes (SWCNTs).
- Activation of TGF-β release and activity via the photothermal effect induced by near-infrared light irradiation.
- Assessment of downstream signal transduction activation and cellular behavior modulation in live cells.
- Preliminary in vivo studies in living mice.
Main Results:
- Near-infrared light successfully triggered the release of active TGF-β from SWCNTs through photothermal effect.
- The released TGF-β effectively activated downstream signaling pathways in live cells.
- Modulation of cellular behaviors, including growth, migration, and differentiation, was observed.
- Preliminary data indicate successful mediation of TGF-β signaling in living mice.
Conclusions:
- SWCNT-assisted near-infrared light activation provides a non-invasive method to control TGF-β signaling.
- This approach offers enhanced spatiotemporal control over a key signaling pathway with potential therapeutic applications.
- The technology demonstrates promise for future research in developmental biology, cancer, and regenerative medicine.
