Researchers at FAMU-FSU College of Engineering have developed a novel technique for examining protein degradation within immune cells that employs engineered microparticles to monitor and evaluate degradation processes more efficiently than conventional approaches.

This research, published in ACS Applied Materials & Interfaces, holds significant ramifications for the treatment of conditions such as cancer, Alzheimer’s disease, and autoimmune ailments.

“There is still much we do not understand about how cells ingest and eliminate tissue debris or pathogens — the process known as phagocytosis,” stated Jingjiao Guan, a professor in the Department of Chemical and Biomedical Engineering and co-author of the paper. “Through this investigation, we aspire to present a new instrument that assists scientists in comprehending this process more effectively.”

This research concentrates on how proteins and peptides decompose within phagosomes — specialized compartments inside immune cells responsible for dismantling ingested foreign particles or deceased cells. While phagosomes play a pivotal role in numerous immune responses, the precise mechanisms of protein and peptide degradation within them remain unclear.

The method established by Guan’s laboratory utilizes engineered particles with fluorescent markers that enable researchers to observe their breakdown and formation into phagosome-derived vesicles, or PDVs. This technique provides a real-time perspective on how immune cells manage proteins and peptides, yielding valuable insights into immune system functioning and dysfunction.

HOW IT FUNCTIONS
Historically, scientists have investigated phagocytosis by utilizing tiny beads made of plastic and silica that are coated with proteins or peptides.

While these bead-based methodologies are beneficial, they come with certain restrictions. Each bead can only accommodate a single layer of protein or peptide, and the beads themselves do not contribute much beyond providing a surface for the protein.

The key innovation created by Guan’s lab was the development of microparticles that emulate natural biological structures.

These engineered particles can incorporate one or several types of proteins or peptides alongside other materials into a precisely defined layered structure, rendering them particularly advantageous for replicating the intricate composition and structure of real-world particles.

The team employed advanced microfabrication techniques to combine proteins and peptides with the polymer poly(N-isopropylacrylamide), or PNIPAM, within the microparticles. This polymer features unique responsive characteristics, making it an excellent tool for tracking and controlling microparticle behavior under varying conditions such as temperature.

Guan’s strategy allows microparticles to be consumed and processed by immune cells, providing a distinctive model for exploring cellular degradation mechanisms.

WHY IT IS SIGNIFICANT
This research carries considerable importance for the medical domain, particularly in understanding immune system activity in conditions such as cancer, spinal cord injuries, and neurodegenerative diseases like Alzheimer’s. By introducing a novel method to analyze protein degradation within immune cells, Guan’s study lays the groundwork for more profound investigations into immune responses and potential therapeutic approaches.

“Understanding where proteins travel and the extent of their degradation during phagocytosis within the cells is crucial for comprehending this process,” remarked Guan.

One of the most promising facets of this research is its potential application to Alzheimer’s disease. The next phase for the team involves studying the degradation of the amyloid beta peptide, a protein linked to Alzheimer’s, utilizing their engineered microparticles. This may yield new insights into the disease’s progression and help identify targets for possible therapeutic intervention.

INTERDISCIPLINARY COLLABORATION AND FUTURE ADVANCEMENTS
Researchers from the FAMU-FSU College of Engineering joined forces with the FSU College of Medicine for this research.

“Working with Dr. Guan has been an exhilarating opportunity to merge engineering with medicine,” noted Yi Ren, a professor in the College of Medicine and co-author of the paper. “This groundbreaking method for studying immune cell behavior is a considerable advancement toward deeper comprehension of disease mechanisms.”

Guan and his team are currently pursuing grants to advance their research and broaden their investigation of microparticle applications in immune system-related disorders.

The particles can be employed with any protein or peptide that can be purified and dissolved in water, making them versatile tools for examining a wide array of biological materials. Previously, comprehensive studies comparing how various types of immune cells decompose different proteins and peptides within phagosomes have been lacking, a study now feasible with this engineered microparticle.

By refining their methodologies and exploring further applications, the researchers aim to contribute to the development of treatments for additional immune and neurodegenerative diseases.

“Collaborating with Dr. Guan has proven to be an immensely gratifying experience,” stated co-author and doctoral candidate Masahiro Fukuda. “Our investigation offers new insights that possess the potential to revolutionize our understanding and treatment of a variety of diseases.”

Co-authors of this publication include Grace Lin, Sailesti Joshi, and Sailesti Joshi from the FAMU-FSU College of Engineering, along with Yang Liu, Grace Hammel, Abigail Kizer, and Maryam Ayazi from the FSU College of Medicine.

This study received funding from the National Institutes of Health.

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