FAMU-FSU College of Engineering researchers have created a new method for studying protein degradation within immune cells that uses engineered microparticles to track and analyze degradation processes more effectively than traditional methods.
The work, which was published in ACS Applied Materials & Interfaces , has important implications for treating diseases such as cancer, Alzheimer's disease and autoimmune disorders.
"There is a lot we still don't know about how cells ingest and eliminate tissue debris or pathogens — the process of phagocytosis," said Jingjiao Guan, a professor in the Department of Chemical and Biomedical Engineering and a paper co-author. "Through this study, we hope to provide a new tool to help scientists better understand this process."
This study focuses on understanding how proteins and peptides degrade within phagosomes — specialized compartments inside immune cells responsible for breaking down engulfed foreign particles or dead cells. Despite the crucial role of phagosomes in numerous immune responses, the exact mechanisms of how proteins and peptides degrade within them have remained unclear.
The approach pioneered by Guan's lab uses engineered particles with fluorescent markers that allow researchers to observe their breakdown and formation into phagosome-derived vesicles, or PDVs. This method provides a real-time view of how immune cells process proteins and peptides, offering valuable insights into immune system function and dysfunction.
HOW IT WORKS
Scientists have traditionally studied phagocytosis by using tiny plastic and silica beads that are coated with proteins or peptides.
Although these bead-based methods are useful, they have some limitations. Each bead can only have a single layer of protein or peptide on it, and the beads themselves don't do much beyond serving as a surface for the protein.
The primary innovation developed by Guan's lab was developing microparticles that mimic natural biological structures.
These engineered particles can incorporate one or more types of proteins or peptides along with other materials into a well-defined layered structure, making them particularly valuable for mimicking the complex composition and structure of real-life particles.
The team used advanced microfabrication techniques to combine proteins and peptides with the polymer poly(N-isopropylacrylamide), or PNIPAM, in microparticles. This polymer exhibits unique responsive properties, making it an ideal tool for tracking and controlling microparticle activity under different conditions like temperature.
Guan's approach enables microparticles to be engulfed and processed by immune cells, providing a unique model for studying cellular degradation mechanisms.
WHY IT MATTERS
This research has significant implications for the medical field, particularly in understanding immune system behavior in diseases such as cancer, spinal cord injuries and neurodegenerative disorders like Alzheimer's. By demonstrating a new method to analyze protein degradation within immune cells, Guan's study paves the way for deeper exploration of immune responses and potential therapeutic strategies.
"Knowing where proteins go and how much they are degraded when they undergo phagocytosis within cells is key to understanding this process," Guan said.
One of the most promising aspects of the research is its potential application to Alzheimer's disease. The team's next phase involves investigating the degradation of the amyloid beta peptide, a protein associated with Alzheimer's, using their engineered microparticles. This could offer new insights into the disease's progression and identify targets for therapeutic intervention.
INTERDISCIPLINARY COLLABORATION AND FUTURE APPLICATIONS
Researchers from the FAMU-FSU College of Engineering collaborated with the FSU College of Medicine for this study.
"Collaborating with Dr. Guan has been an exciting opportunity to bridge engineering and medicine," said Yi Ren, a professor in the College of Medicine and paper co-author. "This innovative approach to studying immune cell behavior is a significant step toward understanding disease mechanisms at a deeper level."
Guan and his team are applying for grants to further their research and expand their study of microparticle applications in immune system-related diseases.
The particles can be used with any protein or peptide that can be purified and dissolved in water, making them useful tools for studying all manner of biological materials. There hasn't been a comprehensive study comparing how different types of immune cells break down various proteins and peptides inside phagosomes, something that is now possible with this engineered microparticle.
By refining their techniques and exploring additional applications, the researchers hope to contribute to the development of treatment for more immune and neurodegenerative disorders.
"Working alongside Dr. Guan has been an incredibly rewarding experience," said paper co-author and doctoral candidate Masahiro Fukuda. "Our study provides new insights that have the potential to transform how we understand and treat various diseases."
Co-authors on this paper included Grace Lin, Sailesti Joshi and Sailesti Joshi from the FAMU-FSU College of Engineering and Yang Liu, Grace Hammel, Abigail Kizer and Maryam Ayazi from the FSU College of Medicine.
This research was supported by the National Institutes of Health.
