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Mechanosensation and Mechanotransduction in Brain Cells

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 12464

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Special Issue Editor

Dr. Chen Gu

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Guest Editor

Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA
Interests: voltage-gated ion channel; mechanosensitive ion channel; molecular motor protein; microtubule-binding protein; axon; myelin; intrinsic excitability; neuron-glia interaction; cognition; inflammation and neurodegeneration; multiple sclerosis; traumatic brain injury; Alzheimer's disease and addiction

Special Issue Information

Dear Colleagues,

Mechanosensation and mechanotransduction are traditionally studied in specialized cell types, such as sensory axonal terminals in the peripheral nervous system, cochlear hair cells in the auditory system, and epithelial cells in the kidney. Recent studies suggest that most, if not all, types of cells possess the ability to convert mechanical stress to electrical or chemical signals, but their underlying mechanisms remain poorly understood. For instance, since the vertebrate brain is well-protected by the skull, its structure and function in the context of mechanics have not been extensively investigated. The brain is the most complex organ in the body, consisting of neuronal and glial cells, as well as endothelial, epithelial, and even immune cells. A better understanding of how these cells sense and respond to mechanical stress could inform new rational therapies for mild traumatic brain injury and related neurodegenerative disorders. For this Special Issue, we welcome original submissions exploring novel phenomena, methodologies, mechanisms, related disorders or animal models of mechanosensation, and mechanotransduction of various cell types in the brain and other organs.

Dr. Chen Gu
Guest Editor

Manuscript Submission Information

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Keywords

mechanosensation
mechanotransduction
ion channel
cytoskeleton
cell adhesion molecule
neuron
glia
lymphocyte
epithelial
endothelial

Published Papers (3 papers)

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Research

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18 pages, 3902 KiB

Open AccessArticle

Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model

by Ajay Vikram Singh, Vaisali Chandrasekar, Peter Laux, Andreas Luch, Sarada Prasad Dakua, Paolo Zamboni, Amruta Shelar, Yin Yang, Vaibhav Pandit, Veronica Tisato and Donato Gemmati

Cells 2022, 11(18), 2801; https://doi.org/10.3390/cells11182801 - 8 Sep 2022

Cited by 22 | Viewed by 3854

Abstract

A hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet–outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte–endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus. Full article

(This article belongs to the Special Issue Mechanosensation and Mechanotransduction in Brain Cells)

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20 pages, 5800 KiB

Open AccessFeature PaperArticle

The Mechanical Microenvironment Regulates Axon Diameters Visualized by Cryo-Electron Tomography

by Di Ma, Binbin Deng, Chao Sun, David W. McComb and Chen Gu

Cells 2022, 11(16), 2533; https://doi.org/10.3390/cells11162533 - 15 Aug 2022

Cited by 5 | Viewed by 2792

Abstract

Axonal varicosities or swellings are enlarged structures along axon shafts and profoundly affect action potential propagation and synaptic transmission. These structures, which are defined by morphology, are highly heterogeneous and often investigated concerning their roles in neuropathology, but why they are present in the normal brain remains unknown. Combining confocal microscopy and cryo-electron tomography (Cryo-ET) with in vivo and in vitro systems, we report that non-uniform mechanical interactions with the microenvironment can lead to 10-fold diameter differences within an axon of the central nervous system (CNS). In the brains of adult Thy1-YFP transgenic mice, individual axons in the cortex displayed significantly higher diameter variation than those in the corpus callosum. When being cultured on lacey carbon film-coated electron microscopy (EM) grids, CNS axons formed varicosities exclusively in holes and without microtubule (MT) breakage, and they contained mitochondria, multivesicular bodies (MVBs), and/or vesicles, similar to the axonal varicosities induced by mild fluid puffing. Moreover, enlarged axon branch points often contain MT free ends leading to the minor branch. When the axons were fasciculated by mimicking in vivo axonal bundles, their varicosity levels reduced. Taken together, our results have revealed the extrinsic regulation of the three-dimensional ultrastructures of central axons by the mechanical microenvironment under physiological conditions. Full article

(This article belongs to the Special Issue Mechanosensation and Mechanotransduction in Brain Cells)

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Review

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35 pages, 5199 KiB

Open AccessFeature PaperReview

Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis

by Ilaria Tortorella, Chiara Argentati, Carla Emiliani, Francesco Morena and Sabata Martino

Cells 2022, 11(19), 3093; https://doi.org/10.3390/cells11193093 - 1 Oct 2022

Cited by 9 | Viewed by 4746

Abstract

In this review, we shed light on recent advances regarding the characterization of biochemical pathways of cellular mechanosensing and mechanotransduction with particular attention to their role in neurodegenerative disease pathogenesis. While the mechanistic components of these pathways are mostly uncovered today, the crosstalk between mechanical forces and soluble intracellular signaling is still not fully elucidated. Here, we recapitulate the general concepts of mechanobiology and the mechanisms that govern the mechanosensing and mechanotransduction processes, and we examine the crosstalk between mechanical stimuli and intracellular biochemical response, highlighting their effect on cellular organelles’ homeostasis and dysfunction. In particular, we discuss the current knowledge about the translation of mechanosignaling into biochemical signaling, focusing on those diseases that encompass metabolic accumulation of mutant proteins and have as primary characteristics the formation of pathological intracellular aggregates, such as Alzheimer’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis and Parkinson’s Disease. Overall, recent findings elucidate how mechanosensing and mechanotransduction pathways may be crucial to understand the pathogenic mechanisms underlying neurodegenerative diseases and emphasize the importance of these pathways for identifying potential therapeutic targets. Full article

(This article belongs to the Special Issue Mechanosensation and Mechanotransduction in Brain Cells)

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