EVs: cellular communication chords
Cells communicate using signaling systems that differ in specificity, timing, and interpretability. Cytokines and growth factors are often “clear” signals: defined molecules released into the extracellular space that bind cognate receptors and trigger comparatively well-mapped intracellular pathways. Extracellular vesicles (EVs), including exosomes and microvesicles, can also influence cell behavior, but their biology makes them especially suited to context-setting modulation (“mood music”) and, in many cases, less suited to delivering a single unambiguous instruction.
Cytokines and growth factors as (reltaively) simple cellular language
Cytokines and growth factors are typically single ligands (or defined ligand families) whose effects are strongly shaped by:
- Receptor specificity (only receptor-expressing cells respond)
- Concentration and exposure time (graded dose–response behavior)
- Mechanistic pathways that are often reproducible across experiments and models
Because the signal is relatively “atomic” (one ligand, known receptor, known downstream pathway), it’s easier to interpret cause-and-effect. This is one reason cytokines and growth factors are widely used as experimental perturbations and clinical biomarkers: they lend themselves to quantification and causal modeling.
EVs as multicomponent “packages”
EVs are fundamentally different: they are membrane-bound particles released by cells and containing mixed cargo; proteins, lipids, and nucleic acids including mRNA and microRNA, and in many contexts EV-associated DNA has been reported.
This cargo diversity is powerful because EVs can, in principle, influence multiple pathways at once. But it also makes EV effects harder to treat as a single “message.” EVs are better thought of as state vectors: they can shift a recipient cell’s baseline settings, gene expression programs, receptor abundance, stress responses, rather than instructing one immediate action.
How EVs “elicit other communication” without being a clean signal themselves
EVs can reshape classical signaling (including cytokine and growth factor signaling) in several evidence-supported ways:
- Surface interactions that trigger signaling
EV membranes display proteins and other molecules that can interact with recipient-cell surfaces. These interactions can activate pathways without requiring the EV to deliver cargo into the cytosol. - Uptake and intracellular rewiring
EV uptake can occur through multiple routes (e.g., endocytic pathways, macropinocytosis, phagocytosis-like processes), and the mechanism varies by EV type and recipient cell. Uptake can lead to downstream transcriptional changes that alter how cells respond to cytokines and growth factors already present in the environment, effectively changing “gain” and “threshold” rather than issuing a single command. - Network-level priming
Because EV exposure can adjust responsiveness, it may “prime” cells so that subsequent cytokine or growth factor stimulation produces stronger, weaker, or qualitatively different outputs. This way EVs can elicit other forms of intercellular communication: by changing the conditions under which those other signals act.
The limitations: why EVs often look like “mood music”
The same features that make EVs rich in information also limit their ability to provide clean, deterministic signaling:
- Heterogeneity of EV populations
Even EVs from the same cell type can be heterogeneous in size, composition, and functional potency. This complicates “one EV = one message” interpretations and is a major theme in modern EV literature. - Biogenesis and classification constraints
EV biogenesis routes overlap, and in practice it can be difficult to claim that a specific effect is unique to a narrowly defined EV subtype (e.g., “exosomes” with “exquisite and specific activities”) without extensive controls. The MISEV guidelines emphasize careful characterization and caution against over-specific functional claims. - Variable delivery efficiency of RNA cargo
EVs clearly carry RNA (including mRNA and miRNA), but the frequency and magnitude of functional RNA delivery—and the extent to which it drives physiological outcomes—can vary widely by model and experimental design. Reviews highlight both strong evidence in some systems and important methodological caveats.
A balanced comparison
Cytokines and growth factors often act like clear sentences: specific ligands, defined receptors, and relatively predictable pathway engagement. EVs more often resemble background music: multi-instrument, context-dependent, and capable of shifting mood, sensitivity, and network behavior. That doesn’t make EVs less important. Their biological niche may be less about issuing a single instruction and more about encoding state (stress, activation, disease) and shaping how other signals are heard and acted upon.
Beyond initiating signaling events, EVs can alter how recipient cells interpret future signals. RNA cargo, particularly microRNAs, can modulate the expression of receptors, ion channels, and intracellular signaling intermediates. As a result, cells may become more or less responsive to cytokines, hormones, or growth factors they subsequently encounter.
This indirect mode of communication is especially important because it introduces longer-term changes in cellular behavior, extending beyond the immediate presence of EVs.
IMAGE Piano keyboard CREDIT Mozzih
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