Due to the highly complex chemical environment within cells and their extreme sensitivity to external stimuli, achieving molecular transformations, especially large macromolecular synthesis, through chemical means within living cells has been challenging. The development of methods for in situ synthesis of macromolecules within cells presents novel avenues for research in cell biology and medicine, holding immense potential.
On March 21st, in the latest research published in Nature Protocols, a team led by Dr. Jin Geng from the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, unveiled their groundbreaking achievement. The team demonstrated a method for in situ macromolecular synthesis within living cells mediated by light, offering new avenues and insights for research in enhancing actin polymerization, modulating intracellular microenvironments, biological imaging applications, and cancer treatment strategies.
The researchers illustrated how high biocompatible monomers were introduced into living cells and polymerization reactions were initiated via light activation, such as reversible addition-fragmentation chain transfer or radical polymerization. Light activation enables precise spatial and temporal control over the polymerization process, exhibiting rapid reaction kinetics and good biocompatibility. The synthesis of different structures of macromolecular polymers typically requires only a few minutes (usually determined by wavelength, approximately 5 to 10 minutes), a brief reaction time crucial for avoiding cellular stress and denaturation of cellular contents.
According to reports, the macromolecular polymers synthesized within cells hold broad potential applications. The increase in cellular viscosity resulting from intracellular macromolecular polymerization can profoundly impact actin polymerization, cellular structure, cell cycle regulation, and cell migration behavior. By using specific monomers for in situ polymerization, they can also serve as biosensors and contrast agents for biological imaging, achieving long-term tracking of cells, a task typically challenging for small molecules.
More importantly, the research team discovered that some monomers, as precursor drugs, can induce cancer cell cycle arrest, autophagy, apoptosis, and necrotic cell death through polymerization, as well as reduce the ability of cancer cells to migrate and move.
Apart from cancer therapy, the construction of this intracellular macromolecular polymerization methodology holds great potential in stem cell research and neurodegenerative disease fields. For instance, by understanding the fundamental mechanisms of intracellular polymerization, researchers can finely manipulate the intracellular environment, potentially influencing stem cell differentiation processes; the mechanisms of intracellular polymerization could be utilized to address protein misfolding and aggregation issues relevant to neurodegenerative disease research; the use of diverse peptide sequences or monomers containing inorganic elements could further expand the potential of intracellular polymerization, unlocking a wide range of possibilities for tailored biomedical applications.
"In summary, the ability to produce customized functional macromolecular polymers within cells brings us closer to advanced therapeutic strategies and innovative biological imaging methods," said Dr. Jin Geng, the corresponding author of the paper and a researcher at the Shenzhen Institutes of Advanced Technology.
Related Paper Information: https://www.nature.com/articles/s41596-024-00970-8
