Neurons under tension: A study of vesicle dynamics

Neurons are the basic communication element in the nervous system of nearly all animals. They communicate with other neurons and other types of cells via chemical and/or electrical signaling. For instance: Our thoughts are processed by a complex network of neurons in our brains; Our vision is mediated by light sensitive optical neurons in our eyes; We move our bodies by actuating muscles signaled by motor neurons; And we are able to sense using sensory neurons wired throughout our bodies. Growing experimental evidence suggests that mechanical tension plays a significant role in determining the growth, guidance, and function of neurons. Recent developments in experimental techniques have made quantitative studies at the level of individual cells possible. The purpose of this dissertation is to introduce the growing field of cellular neuromechanics and present my Ph.D. research on the dynamics of vesicles in neurons under tension. To understand the role of mechanics in neuron function, we must take a closer look at the underlying subcellular dynamics. The basic goal of this research is to explore the currently unknown relationship between applied mechanical strain and vesicle transport in neurons. Vesicle transport in neurons is a critical process since it is necessary for neurotransmission, growth, synaptic plasticity, and several other functions. Thus understanding how mechanical strain affects vesicle transport will shed light on its role in neuronal function (and dysfunction in neurodegenerative diseases). In this dissertation I will discuss: A method for applying mechanical strain to cells; A technique for analyzing nonequilibrium vesicle dynamics; And our main scientific findings that mechanical tension in neurons modulates synaptic vesicle clustering at the Drosophila neuromuscular junction and active transport of vesicles in Aplysia neurons.