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PNAS 106 (31): 12611-12616

Copyright © 2009 by the National Academy of Sciences.


Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

Scott Siechena, Shengyuan Yangb,c, Akira Chibaa,d, and Taher Saifb,1

Departments of aCell and Developmental Biology and bMechanical Science and Engineering, University of Illinois, Urbana, IL 61801; cMechanical and Aerospace Engineering, Florida Institute of Technology, Melbourne, FL 32901; and dDepartment of Biology, University of Miami, Coral Gables, FL 33146

Edited by L. B. Freund, Brown University, Providence, RI, and approved June 11, 2009

Received for publication February 19, 2009.

Abstract: Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynaptic cell. Our in vivo experiments on the embryonic Drosophila nervous system show that vesicle clustering at the neuromuscular presynaptic terminal depends on mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored when mechanical tension is applied to the severed end of the axon. Clustering increases when intact axons are stretched mechanically by pulling the postsynaptic muscle. Using micro mechanical force sensors, we find that embryonic axons that have formed neuromuscular junctions maintain a rest tension of {approx}1 nanonewton. If the rest tension is perturbed mechanically, axons restore the rest tension either by relaxing or by contracting over a period of {approx}15 min. Our results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation and synaptic plasticity.

Key Words: MEMS • neuron • synapse • synaptic vesicle

Freely available online through the PNAS open access option.

Author contributions: S.S., S.Y., A.C., and T.S. designed research; S.S., S.Y., A.C., and T.S. performed research; S.S. and S.Y. contributed new reagents/analytic tools; S.S., S.Y., A.C., and T.S. analyzed data; and A.C. and T.S. wrote the paper.

This article is a PNAS Direct Submission.

This article contains supporting information online at

1To whom correspondence should be addressed. E-mail: saif{at}

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