Novel Method Tracks Phagosomal Protein Breakdown, Advancing Disease Research

Researchers at the FAMU-FSU College of Engineering have developed a new method for studying protein degradation in immune cells, using engineered microparticles that offer a more precise and dynamic way to track these processes than traditional techniques.

Their findings, published in ACS Applied Materials & Interfaces, could have major implications for understanding and treating diseases like cancer, Alzheimer’s, and autoimmune disorders.

“There’s still so much we don’t know about how cells ingest and clear tissue debris or pathogens during phagocytosis. Through this study, we hope to offer scientists a new tool to explore these critical processes.”

— Jingjiao Guan, Professor and Study Co-Author, Department of Chemical and Biomedical Engineering

A Closer Look at Phagosome Activity

The research focuses on protein and peptide degradation within phagosomes—specialized compartments in immune cells that break down engulfed pathogens or dead cells. Despite their central role in immune defense, the exact mechanisms behind protein breakdown in phagosomes remain poorly understood.

Guan’s lab introduced a technique that uses engineered particles embedded with fluorescent markers, allowing researchers to observe degradation events and the formation of phagosome-derived vesicles (PDVs) in real time. This method provides a clearer picture of how immune cells manage protein and peptide processing, offering deeper insight into both healthy and dysfunctional immune responses.

How It Works

Historically, phagocytosis has been studied using plastic or silica beads coated with a single layer of proteins or peptides. While effective to a point, these traditional beads are limited—they can’t carry multiple materials, and mainly serve as a passive surface for the protein.

Guan’s team designed microparticles that better mimic the structure of natural biological materials. These particles can incorporate several types of proteins, peptides, and other substances in a layered format, closely resembling the complexity of actual biological targets.

Using advanced microfabrication, the researchers embedded proteins and peptides within a polymer called poly(N-isopropylacrylamide) (PNIPAM). Known for its responsiveness to environmental changes like temperature, PNIPAM makes it possible to control and track particle behavior under varying lab conditions.

These microparticles are readily engulfed by immune cells, offering a novel model to study the cellular breakdown of proteins in real-world scenarios.

Why This Matters

This research opens new avenues for investigating immune system behavior in diseases ranging from cancer and spinal cord injuries to neurodegenerative conditions like Alzheimer’s.

“Understanding where proteins go and how much they’re broken down during phagocytosis is essential,” said Guan. “It helps us grasp the broader mechanisms of immune function and dysfunction.”

One especially promising direction is applying this method to Alzheimer’s research. In the next phase of their study, the team plans to investigate the degradation of amyloid beta peptide—a protein strongly associated with Alzheimer’s—using their engineered particles. Insights from this work could offer a better understanding of disease progression and potential therapeutic targets.

Cross-Disciplinary Collaboration and What’s Next

The project brought together researchers from the joint engineering college and the FSU College of Medicine.

“Working with Dr. Guan has been a great opportunity to bridge engineering and medicine,” said Yi Ren, Professor and Study Co-Author. “This approach to studying immune cells brings us closer to understanding disease mechanisms at a deeper level.”

The team is currently seeking additional funding to expand their research, particularly into how these microparticles can be used to study other immune-related conditions. Since the particles can be adapted to carry any water-soluble protein or peptide, they offer a flexible platform for investigating a wide range of biological materials.

Until now, no comprehensive study has compared how different types of immune cells degrade a variety of proteins and peptides within phagosomes. This work fills that gap and sets the stage for broader applications.

“Collaborating with Dr. Guan has been incredibly rewarding,” said Masahiro Fukuda, doctoral candidate and study co-author. “Our research offers new insights that could reshape how we understand and treat a range of diseases.”