Exploring the role of chemical biology in unlocking the secrets of extracellular vesicles

In the world of biology, there exist tiny, yet mighty messengers known as extracellular vesicles (EVs). These nano-sized vesicles, secreted by cells, contain a treasure trove of cellular components, including proteins, nucleic acids, and lipids. Emerging research has illuminated the pivotal role of EVs in both health and disease, positioning them as promising candidates for biomarkers and regulators of biological processes.Despite their potential, the analysis of EVs poses unique challenges. Their small size and complex composition make detection and isolation from body fluids a daunting task. However, recent advancements in chemical biology have paved the way for innovative approaches to overcome these obstacles and delve deeper into the mysteries of EV biology.

Over the past decade, researchers have witnessed remarkable progress in the development of technologies for the rapid and sensitive analysis of EVs. Yet, the quest to isolate and detect specific EVs within complex biological fluids persists. Enter chemical biology, a burgeoning field that harnesses the power of chemistry to unravel biological phenomena.

Chemical biology offers a diverse toolkit of molecular probes, labeling techniques, and analytical methods that can be tailored to enhance the study of EVs. By leveraging these tools, researchers can gain insights into the molecular contents of EVs with unprecedented precision and sensitivity.

Researchers at Kangwon National University explored the myriad ways in which chemical biology has advanced our understanding of EV biology. From novel labeling strategies to sophisticated analytical platforms, they researchers delve into the innovative techniques that have revolutionized the field.

exosomes

(A) Intracellular pathways of EV biogenesis, biological functions of EVs, and their analysis. EVs are generated either through the outward budding of plasma membrane (forming ectosomes, microvesicles and apoptotic bodies) or through the inward budding of the endosomal membrane (forming exosomes). Once secreted into the systemic circulation, EVs mediate intercellular communication by transferring their biomolecules between distant cells. Analyzing EVs in biological fluids can help to determine the stage of disease by profiling various EV biomarkers, including proteins, nucleic acids, metabolites, and lipids. (B) Experimental process of EV profiling. Biological fluids are obtained from patients, and processed prior to the EV enrichment step. EVs can be enriched from the similarly sized non-EV particles by various methodsinclude ultracentrifugation, density-gradient centrifugation, size-exclusion chromatography and precipitation. The isolated EVs may require additional sample processing steps to extract analytical targets depends on the downstream detection method. Finally, intact EVs or extracted target analytes are analyzed by various analytical methods for protein and RNA detection.

One key area of focus is the development of molecular probes that selectively target and label EVs, enabling their detection and isolation from complex biological samples. These probes, often engineered with high specificity and affinity, provide researchers with invaluable tools for studying EVs in their native environment.

Furthermore, chemical biology has facilitated the enhancement of conventional assays for EV analysis, improving their sensitivity and accuracy. By integrating chemical modifications and innovative detection methods, researchers can achieve a deeper understanding of EV composition and function.

The integration of chemical biology tools has propelled the study of extracellular vesicles to new heights. By harnessing the power of chemistry, researchers have overcome longstanding challenges and unlocked the potential of EVs as biomarkers and regulators of biological processes.

As the field continues to evolve, the synergy between chemical biology and EV research promises to yield even greater insights into the complex world of intercellular communication. By embracing innovation and collaboration, we can harness the full potential of EVs to advance biomedical research and improve human health.

Lim W, Lee, S Koh M, Jo A, Park .(2024) Recent advances in chemical biology tools for protein and RNA profiling of extracellular vesicles. RSC Chemical Biology [Epub ahead of print]. [abstract]

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