Cells within the body engage in constant communication to maintain health and respond to changes. This communication is not limited to direct contact or soluble factors like hormones. Microscopic packages, known as extracellular vesicles (EVs), play a fundamental role in this cellular dialogue. These tiny messengers travel throughout the body, carrying molecular instructions from one cell to another. Understanding these versatile vesicles sheds light on how cells coordinate functions across biological systems.
Defining Extracellular Vesicles
Extracellular vesicles are microscopic particles released by almost all cell types, enclosed by a lipid bilayer membrane. They vary in size, generally ranging from tens of nanometers to several micrometers. These entities are found in various bodily fluids, including blood, urine, and cerebrospinal fluid. EVs are broadly categorized into three main types based on their origin and size: exosomes, microvesicles, and apoptotic bodies.
Exosomes are typically the smallest (30 to 150 nanometers). Microvesicles, also referred to as ectosomes, are larger (100 to 1,000 nanometers). Apoptotic bodies are the largest (500 to 5,000 nanometers). While these categories help classify EVs, there is some overlap in their characteristics, and research continues to refine their precise definitions.
How Extracellular Vesicles Are Formed
The formation of extracellular vesicles involves distinct cellular processes, depending on their type. Exosomes originate from the endosomal network within a cell. The inner membrane of late endosomes, also known as multivesicular bodies (MVBs), buds inward to form intraluminal vesicles. These MVBs then fuse with the cell’s outer membrane, releasing these vesicles as exosomes into the extracellular space.
Microvesicles, in contrast, form by budding directly outward from the cell’s plasma membrane. This shedding allows microvesicles to encapsulate cellular material. Apoptotic bodies are formed during programmed cell death. As a cell undergoes apoptosis, it disassembles into smaller, membrane-bound fragments, which are released as apoptotic bodies.
The Message Within: EV Cargo
Extracellular vesicles are packed with a diverse array of biomolecules, known as their cargo. This cargo includes proteins, lipids, and nucleic acids. Proteins found within EVs can originate from the cell’s surface, cytoplasm, or even its nucleus.
The nucleic acid content is particularly notable, comprising messenger RNA (mRNA), microRNA (miRNA), and even fragments of DNA. This molecular payload reflects the physiological state of the cell from which the EV originated. For instance, cargo from a stressed cell might differ from that of a healthy cell. The EV’s lipid bilayer membrane protects this delicate cargo from degradation, allowing it to travel and deliver its message intact.
Intercellular Messengers: How EVs Communicate
Extracellular vesicles facilitate communication between cells, whether in close proximity or distant. The mechanisms by which EVs deliver their messages to recipient cells are diverse. One method involves direct fusion, where the EV’s membrane merges with the recipient cell’s plasma membrane, releasing its contents directly into the cell’s interior.
Another common uptake mechanism is endocytosis, where the recipient cell engulfs the EV. EVs can also interact with recipient cells through specific receptor-ligand interactions on the cell surface. Once the EV’s cargo is delivered, it can trigger various changes in the recipient cell, influencing its behavior, gene expression, or overall physiological state.
EVs in Biological Processes
Extracellular vesicles play widespread roles in biological processes, contributing to both normal bodily functions and disease development. In healthy physiological states, EVs are involved in immune responses, tissue repair, and reducing inflammation. They also support cellular homeostasis and development.
In disease contexts, EV-mediated communication can become dysregulated, contributing to pathological conditions. For example, in cancer, tumor cells release EVs that promote tumor growth, shape the surrounding microenvironment, and facilitate metastasis and drug resistance. These tumor-derived EVs transfer aggressive characteristics to recipient cells. In neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, EVs spread toxic misfolded proteins between brain cells. In infectious diseases, pathogens exploit EVs to spread infection or modulate the host’s immune response.