scholarly journals Mechanotransduction in Neuronal Cell Development and Functioning

2019 ◽  
Author(s):  
Matteo Chighizola ◽  
Tania Dini ◽  
Cristina Lenardi ◽  
Paolo Milani ◽  
Alessandro Podestà ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Neuronal Cell ◽  
Cell Development ◽  
Spatial Organisation ◽  
Cell Behaviour ◽  
Cell Microenvironment ◽  
Adhesion Sites ◽  
It Impacts ◽  
Adhesion Complex ◽  
Biophysical Cues

Although many details remain still elusive, it became increasingly evident in recent years that mechanosensing of microenvironmental biophysical cues and subsequent mechanotransduction are strongly involved in the regulation of neuronal cell development and functioning. This review gives an overview about the current understanding of brain and neuronal cell mechanobiology and how it impacts on neurogenesis, neuronal migration, differentiation, and maturation. Therein; we are focussing particularly on the events in the cell/microenvironment interface and the decisive extracellular matrix (ECM) parameters (i.e. rigidity and nanometric spatial organisation of adhesion sites) that modulate integrin adhesion complex-based mechanosensing and mechanotransductive signalling. It will also be outlined how biomaterial approaches mimicking essential ECM features help to understand these processes and how they can be used to control and guide neuronal cell behaviour by providing appropriate biophysical cues. In addition, principal biophysical methods will be highlighted that have been crucial for the study of neuronal mechanobiology.

Fibronexus-Like Adhesion Sites are Present at the Invasive Zones of Human Epidermoid Carcinomas

1982 ◽  
Vol 40 ◽  
pp. 106-109
Author(s):  
Irwin I. Singer
Keyword(s):  
Cell Cycle ◽  
Serum Concentration ◽  
Substrate Binding ◽  
High Serum ◽  
Adhesion Sites ◽  
Substrate Adhesion ◽  
Focal Contacts ◽  
Adhesion Complex ◽  
Low Serum

Our previous results indicate that two types of fibronectin-cytoskeletal associations may be formed at the fibroblast surface: dorsal matrixbinding fibronexuses generated in high serum (5% FBS) cultures, and ventral substrate-adhering units formed in low serum (0.3% FBS) cultures. The substrate-adhering fibronexus consists of at least vinculin (VN) and actin in its cytoplasmic leg, and fibronectin (FN) as one of its major extracellular components. This substrate-adhesion complex is localized in focal contacts, the sites of closest substratum approach visualized with interference reflection microscopy, which appear to be the major points of cell-tosubstrate adhesion. In fibroblasts, the latter substrate-binding complex is characteristic of cultures that are arrested at the G1 phase of the cell cycle due to the low serum concentration in their medium. These arrested fibroblasts are very well spread, flattened, and immobile.

scholarly journals Crucial Roles of the Arp2/3 Complex during Mammalian Corticogenesis

2015 ◽  
Author(s):  
Pei-Shan Wang ◽  
Fu-Sheng Chou ◽  
Fengli Guo ◽  
Praveen Suraneni ◽  
Sheng Xia ◽  
...  
Keyword(s):  
Cell Fate ◽  
Membrane Trafficking ◽  
Neuronal Migration ◽  
Neuronal Cell ◽  
Leading Edge ◽  
Radial Glial Cells ◽  
A Cell ◽  
Radial Glial ◽  
Altered Cell ◽  
Actin Nucleator

The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex, the unique actin nucleator that produces branched actin networks, plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly may be particularly important for neuronal cell motility in soft or poorly adhesive matrix environment.

E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton

1998 ◽  
Vol 111 (8) ◽  
pp. 1071-1080 ◽  
Author(s):  
S.M. Reuver ◽  
C.C. Garner
Keyword(s):  
Cell Adhesion ◽  
Model Systems ◽  
Molecular Organization ◽  
Cell Contact ◽  
Adhesion Sites ◽  
Associated Proteins ◽  
Adhesion Complex ◽  
Cortical Cytoskeleton ◽  
E Cadherin ◽  
Cell Cell

Members of the SAP family of synapse-associated proteins have recently emerged as central players in the molecular organization of synapses. In this study, we have examined the mechanism that localizes one member, SAP97, to sites of cell-cell contact. Utilizing epithelial CACO-2 cells and fibroblast L-cells as model systems, we demonstrate that SAP97 is associated with the submembranous cortical cytoskeleton at cell-cell adhesion sites. Furthermore, we show that its localization into this structure is triggered by E-cadherin. Although SAP97 can be found in an E-cadherin/catenin adhesion complex, this interaction seems to be mediated by the attachment of SAP97 to the cortical cytoskeleton. Our results are consistent with a model in which SAP97 is recruited to sites of cell-cell contact via an E-cadherin induced assembly of the cortical cytoskeleton.

Nano- and Micro-Structured Substrates for Neuronal Cell Development

2005 ◽  
Vol 1 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Furqan Haq ◽  
Yeswanth L. Rao ◽  
Charles Keith ◽  
Yiping Zhao ◽  
Guigen Zhang
Keyword(s):  
Neuronal Cell ◽  
Cell Development

scholarly journals Mechanically Activated Extracellular Vesicle Functionalised Melt Electrowritten Materials for Bone Regeneration: A Mechano-Biomimetic Scaffold

2021 ◽  
Author(s):  
Kian Eichholz ◽  
Angelica Federici ◽  
Mathieu Riffault ◽  
Ian Woods ◽  
Olwyn Mahon ◽  
...  
Keyword(s):  
Bone Repair ◽  
Extracellular Vesicle ◽  
Great Promise ◽  
Cell Behaviour ◽  
Tissue Scaffold ◽  
Biomimetic Scaffold ◽  
Indirect Cues ◽  
Mediate Cell ◽  
Alkaline Phosphatase Expression ◽  
Biophysical Cues

Mechanobiological cues arising directly via tissue/scaffold mechanics or indirectly via mechanically activated cell secretomes represent potent stimuli that mediate cell behaviour and tissue adaptation. Exploiting these cues in regeneration strategies holds great promise for tissue repair. In this study, we harness indirect biophysical cues originating from osteocytes in a combination with direct biophysical cues from Melt ElectroWritten (MEW) scaffolds to form a single engineered construct with the aim of synergistically enhancing osteogenesis. The secretome of mechanically activated osteocytes was collected within conditioned media (CM) and extracellular vesicles (EV) were subsequently isolated. Building on MEW micro-fibrous scaffolds with controlled microarchitecture and mineral nanotopography optimised for bone repair, a protocol was developed to functionalise these materials with CM or EVs. Human MSC proliferation was enhanced in both CM and EV functionalised scaffolds. EV functionalised scaffolds were further found to significantly enhance MSC osteogenesis, with enhanced alkaline phosphatase expression, collagen production, and mineralisation compared to control scaffolds. Furthermore, enhanced formation of mineralised nodules was identified in EV functionalised materials. Combining direct biophysical cues provided by the fibrous architecture/mineral nanotopography with the indirect cues provided by EVs, these constructs hold great promise to enhance the repair of damaged bone in a physiologically relevant manner.

scholarly journals Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

2014 ◽  
Vol 70 (6) ◽  
pp. 1680-1694 ◽  
Author(s):  
Rajesh Ponnusamy ◽  
Andrey A. Lebedev ◽  
Steffen Pahlow ◽  
Bernhard Lohkamp
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Nerve Cell ◽  
Neuronal Cell ◽  
Correlation Coefficients ◽  
Cell Development ◽  
Structural Comparison ◽  
Gene Encoding ◽  
Novel Method ◽  
Insight Into

Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms ofRfactors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of theDPYSL-3gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

scholarly journals Expression of the Antiapoptotic Gene CLN3 in Neuronal Cell Development

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 345A-345A
Author(s):  
Maria A Pane ◽  
Kasturi Puranam ◽  
Rose-Mary Boustany
Keyword(s):  
Neuronal Cell ◽  
Cell Development ◽  
Antiapoptotic Gene

scholarly journals Cell morphology and focal adhesion location alters internal cell stress

2014 ◽  
Vol 11 (101) ◽  
pp. 20140885 ◽  
Author(s):  
C. A. Mullen ◽  
T. J. Vaughan ◽  
M. C. Voisin ◽  
M. A. Brennan ◽  
P. Layrolle ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Cell Morphology ◽  
Computational Models ◽  
Substrate Stiffness ◽  
Osteogenic Cell ◽  
Cell Behaviour ◽  
Internal Cell ◽  
Adhesion Sites ◽  
Cell Processes

Extracellular mechanical cues have been shown to have a profound effect on osteogenic cell behaviour. However, it is not known precisely how these cues alter intracellular mechanics to initiate changes in cell behaviour. In this study, a combination of in vitro culture of MC3T3-E1 cells and finite-element modelling was used to investigate the effects of passive differences in substrate stiffness on intracellular mechanics. Cells on collagen-based substrates were classified based on the presence of cell processes and the dimensions of various cellular features were quantified. Focal adhesion (FA) density was quantified from immunohistochemical staining, while cell and substrate stiffnesses were measured using a live-cell atomic force microscope. Computational models of cell morphologies were developed using an applied contraction of the cell body to simulate active cell contraction. The results showed that FA density is directly related to cell morphology, while the effect of substrate stiffness on internal cell tension was modulated by both cell morphology and FA density, as investigated by varying the number of adhesion sites present in each morphological model. We propose that the cells desire to achieve a homeostatic stress state may play a role in osteogenic cell differentiation in response to extracellular mechanical cues.

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