Editorial: Neuronal Mechanics and Transport

摘要

Past research on nervous system development was largely centered on the role of molecules and biochemical signaling cascades. However, recent biophysical work has clearly demonstrated the additional importance of forces in shaping neuronal morphology and driving intracellular transport as well as the role of stiffness for cellular behavior. The research topic “Neuronal Mechanics and Transport” brings together related research articles and reviews with the long-term goal of fostering a community of scientists interested in this interdisciplinary topic. The shaping of neurons, glia, and the brain The importance of forces in shaping the morphology of the nervous system spans scales ranging from the whole brain down to individual cells and involves both neurons and glia. Budday et al. focus on cortical folding. They briefly review the developmental biology of the human brain and then discuss modeling and experimental work designed to elucidate the mechanisms underlying cortical folding. They emphasize that local differences in stiffness, growth rate, and cellular force balance during normal development lead to the characteristic pattern of folding and discuss how diseases that impact these underlying processes lead to either increases or decreases in the number of folds. Bollmann et al. investigated durotaxis in microglia using traction force microscopy ( Bollmann et al. ). Using experimental and theoretical analysis, they make a compelling argument that microglia preferentially migrate toward stiffer regions because they take larger steps in the direction of the stiffer region. In turn Schwann cells are important for myelinating neurons in the peripheral nervous system. Like neurons, they have an extended geometry and locally synthesize proteins in response to local signals and protein demand. Love and Shah monitored ribosomal transport in Schwann cells by expressing a GFP tagged version of the ribosomal L4 subunit and then developed a rate kinetics model of ribosomal transport. They found that initially levels of transport were high, but then declined as Schwann cells began myelination. Together these studies are important because they remind us that glia are as important as neurons when considering the mechanics of nervous system. Controlling axonal and dendritic length, branching, and diameter Controlling local protein production and long distance transport of material is a major engineering challenge for neurons. A recent idea proposes that neurons can sense the length of axons and in turn control the rate of protein production. This leads to the obvious question of how. Bressloff and Karamched build on the idea, first developed in yeast, that frequency information (i.e., regular variations in the concentration of signaling proteins) is used to regulate the activity of gene networks. They propose that as axons lengthen, the frequency of an encoded signal drops, which in turn alters the rate of material production. This work is important because it points out that as axons lengthen the precision of axonal length measurement may decrease, and it highlights the need for future experimental work. Directly related to the problem of length control is the question of how process branching is regulated. Sholl analysis is an important tool that assesses branching by measuring the number of neuronal processes that pass through concentric circles spaced at fixed internals from the cell body. O'Neill et al. compared Inside-Out, Root-Intermediate-Terminal, and Tips-In Sholl analysis while characterizing the effect of cytosolic PSD-95 interactor (cypin) on the patterning of the dendritic arbors of hippocampal neurons. They found that each approach can detect large changes in branching, but they have regional differences in their sensitivity in detecting subtle variations. They suggest that standard Sholl analysis might be improved by integrating these approaches and by making their use more transparent in software used by biologists. Finally, axons have the remarkable geometrical property of having a relatively uniform diameter over distances that can be as long a meter in humans. How diameter is consistently maintained is especially puzzling as necking (i.e., local thinning) of materials typically occurs in response to large deformations. Two of the founders of the field of neuronal mechanics Heidemann and Bray , propose the novel theory that tension may locally induce breakage and the local compaction of neurofilaments and microtubules. As a result, the transport of cytoskeletal elements along the axon is locally inhibited and material accumulates and allows the axon to return to its original diameter in regions that are locally thin. Together these studies point out the importance of understanding the relationship between neuronal geometry, mechanics, and transport. Brain strain and electrical excitability Most studies on neurons are typically concerned with either mechanical or electrical behavior, yet it has becom