scholarly journals Biophysics and Modeling of Mechanotransduction in Neurons: A Review

Mathematics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 323
Author(s):  
Martina Nicoletti ◽  
Letizia Chiodo ◽  
Alessandro Loppini

Mechanosensing is a key feature through which organisms can receive inputs from the environment and convert them into specific functional and behavioral outputs. Mechanosensation occurs in many cells and tissues, regulating a plethora of molecular processes based on the distribution of forces and stresses both at the cell membrane and at the intracellular organelles levels, through complex interactions between cells’ microstructures, cytoskeleton, and extracellular matrix. Although several primary and secondary mechanisms have been shown to contribute to mechanosensation, a fundamental pathway in simple organisms and mammals involves the presence of specialized sensory neurons and the presence of different types of mechanosensitive ion channels on the neuronal cell membrane. In this contribution, we present a review of the main ion channels which have been proven to be significantly involved in mechanotransduction in neurons. Further, we discuss recent studies focused on the biological mechanisms and modeling of mechanosensitive ion channels’ gating, and on mechanotransduction modeling at different scales and levels of details.

2002 ◽  
Vol 22 (4) ◽  
pp. 1238-1247 ◽  
Author(s):  
Hawon Cho ◽  
Jieun Shin ◽  
Chan Young Shin ◽  
Soon-Youl Lee ◽  
Uhtaek Oh

Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.


2012 ◽  
Vol 14 (3) ◽  
pp. 239-252

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.


2019 ◽  
Vol 15 (5) ◽  
pp. 486-495 ◽  
Author(s):  
Li-Xin Peng ◽  
Xue-Hui Liu ◽  
Bo Lu ◽  
Si-Ming Liao ◽  
Feng Zhou ◽  
...  

Background:The polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface Of Neuronal Cell Adhesion Molecule (NCAM) in a number of cancer cells, and strongly correlates with the migration and invasion of tumor cells and with aggressive, metastatic disease and poor clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX). Selective inhibition of polySTs, therefore, presents a therapeutic opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. Heparin has been found to be effective in inhibiting the ST8Sia IV activity, but no clear molecular rationale. It has been found that polysialyltransferase domain (PSTD) in polyST plays a significant role in influencing polyST activity, and thus it is critical for NCAM polysialylation based on the previous studies.Objective:To determine whether the three different types of heparin (unfractionated hepain (UFH), low molecular heparin (LMWH) and heparin tetrasaccharide (DP4)) is bound to the PSTD; and if so, what are the critical residues of the PSTD for these binding complexes?Methods:Fluorescence quenching analysis, the Circular Dichroism (CD) spectroscopy, and NMR spectroscopy were used to determine and analyze interactions of PSTD-UFH, PSTD-LMWH, and PSTD-DP4.Results:The fluorescence quenching analysis indicates that the PSTD-UFH binding is the strongest and the PSTD-DP4 binding is the weakest among these three types of the binding; the CD spectra showed that mainly the PSTD-heparin interactions caused a reduction in signal intensity but not marked decrease in α-helix content; the NMR data of the PSTD-DP4 and the PSTDLMWH interactions showed that the different types of heparin shared 12 common binding sites at N247, V251, R252, T253, S257, R265, Y267, W268, L269, V273, I275, and K276, which were mainly distributed in the long α-helix of the PSTD and the short 3-residue loop of the C-terminal PSTD. In addition, three residues K246, K250 and A254 were bound to the LMWH, but not to DP4. This suggests that the PSTD-LMWH binding is stronger than the PSTD-DP4 binding, and the LMWH is a more effective inhibitor than DP4.Conclusion:The findings in the present study demonstrate that PSTD domain is a potential target of heparin and may provide new insights into the molecular rationale of heparin-inhibiting NCAM polysialylation.


2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Vincenza Conteduca ◽  
Giulia Poti ◽  
Paola Caroli ◽  
Sabino Russi ◽  
Nicole Brighi ◽  
...  

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.


2021 ◽  
Author(s):  
Jung-uk Lee ◽  
Wookjin Shin ◽  
Yongjun Lim ◽  
Jungsil Kim ◽  
Woon Ryoung Kim ◽  
...  

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