Nanocarriers and Intracellular Transport: Moving Along the Cytoskeletal Matrix

Abstract

The cytoskeleton of neurons is the nanoscale matrix along which organelles, proteins, mRNAs, or signaling complexes are guided to their final destinations inside the cell. Nanotechnology and molecular biology have enabled precision study of these biomolecular machines, in some cases down to the level of single molecules. Motor, linker, and adaptor proteins are essential to the transport process – the three main motors being kinesin, dynein, and myosin, each of which give rise to families of related motor proteins. Neurons are unique in that they possess two distinct transport systems: one in the axon and the other in the somatodendritic compartment. Microtubules are the main tracks for transport in the axon shaft, with neurofilaments (also concentrated within axons) stabilizing the microtubule network. Synaptic vesicles, containing biosynthetic enzymes that are responsible for manufacturing and releasing neurotransmitters, are routinely transported down along axonal microtubules towards actin–rich axon terminals. Endosomes incorporating neurotrophins typically travel in the reverse direction, from axon terminal to the cell body. These transport processes have been tracked with quantum dot nanoparticles attached to single motor proteins or individual cargo molecules. Microtubules also fill the somatodendritic compartments of neurons where they are pivotal to the transport of neurotransmitter receptor subunits and mRNAs from the cell body to postsynaptic sites, in particular to spines – the postsynaptic specializations enriched with actin filaments. Levels of synaptic activity affect the transport of neurotransmitter receptors and mRNA, and permanent changes in synaptic strength partly depend on transport to postsynaptic sites. Alterations in axonal and dendritic transport underlie neuronal responses to injury, regeneration and morphogenesis, as well as learning and memory. Modifications of transport tracks may constitute a subcellular memory mechanism by which the altered intraneuronal connectivity contributes to the memory trace. Elucidation of this mechanism of memory will come with a greater understanding of the biophysics of transport and motor protein mechanics. Biophysical models detailing the nanoscale mechanisms of cellular transport have already increased our understanding of how biological motors operate mechanistically, providing fundamental guiding principles for nanotechnological advancements. Potential nanotechnologies expected to result from biophysical studies of biological transport include bioengineered motors and biomimetic nanocarrier devices, both promising to be useful in biomedicine or as analytical devices. Cytoskeletal and motor proteins, or hybrid designs including these proteins, stand to contribute to a wide variety of potential nanostructured products.