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This study develops an exact mathematical solution for modeling vesicle-mediated cellular signaling, where cells communicate by releasing packets of molecules in stochastic bursts that are then degraded over time. The researchers demonstrate that the timing of cellular activation depends not just on average release rates, but critically on the statistical patterns of vesicle arrival events and the variability in burst sizes. Their model reveals that different release patterns with identical mean rates can produce qualitatively different activation behaviors due to time-asymmetric fluctuations in the system.
Why it matters
Understanding the precise statistical nature of vesicle-mediated signaling is essential for neurotransmission and hormone release processes. This framework could inform drug design targeting synaptic transmission disorders and improve predictions of how cells respond to signaling events in both normal physiology and disease states.
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arXiv:2605.06456v2 Announce Type: replace-cross
Abstract: Vesicle-mediated secretion of ions or molecules is a central mechanism of cellular communication, for example in processes such as neurotransmission or hormone release. These events are inherently stochastic: vesicle fusions lead to bursts of variable sizes, releasing discrete packets of transmitters that are subsequently cleared or degraded. The dynamics are intrinsically time-directed due to the interplay of spontaneous bursts and continuous degradation. Using generating functions and a recursion relation, we derive an exact solution for the full time-dependent probability distribution of a general batch arrival degradation model. This framework also enables a full analysis of first-passage times to a concentration threshold representing downstream activation. We show that activation kinetics are not determined by mean dynamics alone, but depend sensitively on the temporal statistics of arrival events, batch-size variability, and degradation. In particular, different arrival processes with identical mean rates can lead to qualitatively distinct first passage behavior, reflecting the role of time-asymmetric fluctuations. We also discuss extensions incorporating vesicle depletion. Our results provide a transparent link between stochastic release dynamics and activation timing in vesicle-mediated signaling.
Source: Activation in Vesicle-Mediated Signaling Shaped by Batch Arrival Statistics