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 Drosophila neuromuscular junction (NMJ) and is actively regulated by neurons both in vitro and in vivo. In this work, we applied mechanical strain on in vivo Drosophila neurons and in vitro Aplysia 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 Drosophila NMJ and (2) the local motion of individual large dense core vesicles (LDCV) in Aplysia neurites. Specifically, a sustained stretch results in enhanced SV accumulation in the Drosophila 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 Aplysia 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.
KeywordsCell mechanics Subcellular Live-imaging Vesicle tracking Drosophila Aplysia
The authors thank Dr. J. Rajagopalan for discussions concerning the manuscript and X. Wang for preparation of neuronal cultures. W. W. Ahmed thanks the Arnold and Mabel Foundation and the Beckman Institute for Advanced Science and Technology for their generous support. This work was supported by the National Institutes of Health (NINDS NS031609, R25 CA154015) and the National Science Foundation (CMMI 0800870, ECCS 0801928, DGE 0965918, CBET 0939511). Microfabrication facilities were used at the Micro and Nanotechnology Laboratory and imaging facilities were used at the Institute for Genomic Biology at the University of Illinois at Urbana-Champaign.
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