Mechanical Tension Modulates Local and Global Vesicle Dynamics in Neurons

Growing experimental evidence suggests that mechanical tension plays a significant role in determining the growth, guidance, and function of neurons. Mechanical tension in axons contributes to neurotransmitter clustering at the neuromuscular junction (NMJ) and is actively regulated by neurons both and . In this work, we applied mechanical strain on neurons and neurons and studied their vesicle dynamics by live-imaging. Our experiments show that mechanical stretch modulates the dynamics of vesicles in two different model systems: (1) The global accumulation of synaptic vesicles (SV) at the NMJ and (2) the local motion of individual large dense core vesicles (LDCV) in neurites. Specifically, a sustained stretch results in enhanced SV accumulation in the NMJ. This increased SV accumulation occurs in the absence of extracellular Ca2+, plateaus after approximately 50 min, and persists for at least 30 min after stretch is reduced. On the other hand, mechanical compression in neurites immediately disrupts LDCV motion, leading to decreased range and processivity. This impairment of LDCV motion persists for at least 15 min after tension is restored. These results show that mechanical stretch modulates both local and global vesicle dynamics and strengthens the notion that tension serves a role in regulating neuronal function.