scholarly journals Axonal growth on surfaces with periodic geometrical patterns

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257659
Author(s):  
Jacob P. Sunnerberg ◽  
Marc Descoteaux ◽  
David L. Kaplan ◽  
Cristian Staii
Keyword(s):  
Network Formation ◽  
Nerve Repair ◽  
Critical Role ◽  
Axonal Growth ◽  
Angular Distributions ◽  
Growth Substrate ◽  
Neuron Networks ◽  
Geometrical Features ◽  
Steering Mechanism ◽  
Fundamental Understanding

The formation of neuron networks is a complex phenomenon of fundamental importance for understanding the development of the nervous system, and for creating novel bioinspired materials for tissue engineering and neuronal repair. The basic process underlying the network formation is axonal growth, a process involving the extension of axons from the cell body towards target neurons. Axonal growth is guided by environmental stimuli that include intercellular interactions, biochemical cues, and the mechanical and geometrical features of the growth substrate. The dynamics of the growing axon and its biomechanical interactions with the growing substrate remains poorly understood. In this paper, we develop a model of axonal motility which incorporates mechanical interactions between the axon and the growth substrate. We combine experimental data with theoretical analysis to measure the parameters that describe axonal growth on surfaces with micropatterned periodic geometrical features: diffusion (cell motility) coefficients, speed and angular distributions, and axon bending rigidities. Experiments performed on neurons treated Taxol (inhibitor of microtubule dynamics) and Blebbistatin (disruptor of actin filaments) show that the dynamics of the cytoskeleton plays a critical role in the axon steering mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which high-curvature geometrical features impart high traction forces to the growth cone. These results have important implications for our fundamental understanding of axonal growth as well as for bioengineering novel substrates that promote neuronal growth and nerve repair.

scholarly journals Neuronal Growth and Formation of Neuron Networks on Directional Surfaces

Biomimetics ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 41
Author(s):  
Ilya Yurchenko ◽  
Matthew Farwell ◽  
Donovan D. Brady ◽  
Cristian Staii
Keyword(s):  
Network Formation ◽  
Nerve Repair ◽  
Critical Role ◽  
Axonal Growth ◽  
Neuronal Growth ◽  
Neural Repair ◽  
Geometrical Properties ◽  
Neuron Networks ◽  
Steering Mechanism ◽  
Directional Surfaces

The formation of neuron networks is a process of fundamental importance for understanding the development of the nervous system and for creating biomimetic devices for tissue engineering and neural repair. The basic process that controls the network formation is the growth of an axon from the cell body and its extension towards target neurons. Axonal growth is directed by environmental stimuli that include intercellular interactions, biochemical cues, and the mechanical and geometrical properties of the growth substrate. Despite significant recent progress, the steering of the growing axon remains poorly understood. In this paper, we develop a model of axonal motility, which incorporates substrate-geometry sensing. We combine experimental data with theoretical analysis to measure the parameters that describe axonal growth on micropatterned surfaces: diffusion (cell motility) coefficients, speed and angular distributions, and cell-substrate interactions. Experiments performed on neurons treated with inhibitors for microtubules (Taxol) and actin filaments (Y-27632) indicate that cytoskeletal dynamics play a critical role in the steering mechanism. Our results demonstrate that axons follow geometrical patterns through a contact-guidance mechanism, in which geometrical patterns impart high traction forces to the growth cone. These results have important implications for bioengineering novel substrates to guide neuronal growth and promote nerve repair.

scholarly journals Formyl Peptide Receptor 1 Modulates Endothelial Cell Functions by NADPH Oxidase-Dependent VEGFR2 Transactivation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Fabio Cattaneo ◽  
Martina Castaldo ◽  
Melania Parisi ◽  
Raffaella Faraonio ◽  
Gabriella Esposito ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Information Exchange ◽  
Network Formation ◽  
Critical Role ◽  
Cellular Migration ◽  
Formyl Peptide Receptor ◽  
Rt Pcr ◽  
Signalling Molecules ◽  
Cell Functions ◽  
Formyl Peptide

In the vasculature, NADPH oxidase is the main contributor of reactive oxygen species (ROS) which play a key role in endothelial signalling and functions. We demonstrate that ECV304 cells express p47phox, p67phox, and p22phox subunits of NADPH oxidase, as well as formyl peptide receptors 1 and 3 (FPR1/3), which are members of the GPCR family. By RT-PCR, we also detected Flt-1 and Flk-1/KDR in these cells. Stimulation of FPR1 by N-fMLP induces p47phox phosphorylation, which is the crucial event for NADPH oxidase-dependent superoxide production. Transphosphorylation of RTKs by GPCRs is a biological mechanism through which the information exchange is amplified throughout the cell. ROS act as signalling intermediates in the transactivation mechanism. We show that N-fMLP stimulation induces the phosphorylation of cytosolic Y951, Y996, and Y1175 residues of VEGFR2, which constitute the anchoring sites for signalling molecules. These, in turn, activate PI3K/Akt and PLC-γ1/PKC intracellular pathways. FPR1-induced ROS production plays a critical role in this cross-talk mechanism. In fact, inhibition of FPR1 and/or NADPH oxidase functions prevents VEGFR2 transactivation and the triggering of the downstream signalling cascades. N-fMLP stimulation also ameliorates cellular migration and capillary-like network formation ability of ECV304 cells.

scholarly journals Interfacial Acidity on Oxide Surfaces: A Scaling Paradigm and the Role of the Hydrogen Bond

2020 ◽  
Author(s):  
Robert Chapleski ◽  
Azhad U. Chowdhury ◽  
Kyle Mason ◽  
Robert Sacci ◽  
Benjamin Doughty ◽  
...  
Keyword(s):  
Density Functional ◽  
Critical Role ◽  
Surface Interactions ◽  
Van Der Waals Interactions ◽  
Chemical Transformations ◽  
Acid Base ◽  
Functional Theory ◽  
Fundamental Understanding ◽  
Molecule Surface

<p><a></a>A fundamental understanding of acidity at an interface, as mediated by structure and molecule-surface interactions, is essential to elucidate the mechanisms of a range of chemical transformations. While the strength­­­­ of an acid in the gas and solution phases is conceptually well understood, how acid-base chemistry works at an interface is notoriously more complicated. Using density functional theory and nonlinear vibrational spectroscopy, we have developed a method to determine the interfacial Brønsted-Lowry acidity of aliphatic alcohols adsorbed on the {100} surface of the model perovskite, strontium titanate. Here we show that, while shorter and less branched alkanols are less acidic as a gas and more acidic in solution, shorter alcohols are less acidic whereas less substituted alkanols are more acidic at the gas-surface interface. Hydrogen bonding plays a critical role in defining acidity, whereas structure-acidity relationships are dominated by van der Waals interactions between the alcohol and the surface.</p><p><a></a></p><p> </p>

Interfacial Acidity on Oxide Surfaces: A Scaling Paradigm and the Role of the Hydrogen Bond

2020 ◽  
Author(s):  
Robert Chapleski ◽  
Azhad U. Chowdhury ◽  
Kyle Mason ◽  
Robert Sacci ◽  
Benjamin Doughty ◽  
...  
Keyword(s):  
Density Functional ◽  
Critical Role ◽  
Surface Interactions ◽  
Van Der Waals Interactions ◽  
Chemical Transformations ◽  
Acid Base ◽  
Functional Theory ◽  
Fundamental Understanding ◽  
Molecule Surface

<p><a></a>A fundamental understanding of acidity at an interface, as mediated by structure and molecule-surface interactions, is essential to elucidate the mechanisms of a range of chemical transformations. While the strength­­­­ of an acid in the gas and solution phases is conceptually well understood, how acid-base chemistry works at an interface is notoriously more complicated. Using density functional theory and nonlinear vibrational spectroscopy, we have developed a method to determine the interfacial Brønsted-Lowry acidity of aliphatic alcohols adsorbed on the {100} surface of the model perovskite, strontium titanate. Here we show that, while shorter and less branched alkanols are less acidic as a gas and more acidic in solution, shorter alcohols are less acidic whereas less substituted alkanols are more acidic at the gas-surface interface. Hydrogen bonding plays a critical role in defining acidity, whereas structure-acidity relationships are dominated by van der Waals interactions between the alcohol and the surface.</p><p><a></a></p><p> </p>

scholarly journals Electrospun Hyaluronan-Gelatin Nanofibrous Matrix for Nerve Tissue Engineering

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hau-Min Liou ◽  
Lih-Rou Rau ◽  
Chun-Chiang Huang ◽  
Meng-Ru Lu ◽  
Fu-Yin Hsu
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Cell Attachment ◽  
Nerve Repair ◽  
Critical Role ◽  
Nerve Tissue ◽  
Growth Environment ◽  
Biological Performance ◽  
Electrospun Gelatin

Schwann cells play a critical role in the repair of the peripheral nerve. The goal of this study was to fabricate electrospun gelatin (Gel) and hyaluronan-gelatin (HA-Gel) composite nanofibers to provide a suitable growth environment for Schwann cells. The fiber diameters of Gel, 0.5 HA-Gel, 1 HA-Gel, and 1.5 HA-Gel were 130 ± 30 nm, 294 ± 87 nm, 362 ± 129 nm, and 224 ± 54 nm, respectively. The biological performance of Gel and HA-Gel was evaluated using anin vitroculture of RT4-D6P2T rat Schwann cells. We found that the cell attachment and proliferation rates were not significantly different on these matrices. However, the Schwann cells displayed better organized F-actin on HA-Gel than on Gel. Moreover, the expression levels of several genes, including Nrg1, GFAP, and P0, were significantly higher on HA-Gel than on Gel. In addition, the levels of Nrg1 and P0 protein expression were also higher on the HA-Gel than on Gel. These results indicate that the hyaluronan-gelatin composite nanofibrous matrix could potentially be used in peripheral nerve repair.

scholarly journals Regulation of Notch1 and Dll4 by Vascular Endothelial Growth Factor in Arterial Endothelial Cells: Implications for Modulating Arteriogenesis and Angiogenesis

2003 ◽  
Vol 23 (1) ◽  
pp. 14-25 ◽  
Author(s):  
Zhao-Jun Liu ◽  
Takashi Shirakawa ◽  
Yan Li ◽  
Akinobu Soma ◽  
Masahiro Oka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Notch Signaling ◽  
Network Formation ◽  
Critical Role ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Arterial Endothelial Cells

ABSTRACT Notch and its ligands play critical roles in cell fate determination. Expression of Notch and ligand in vascular endothelium and defects in vascular phenotypes of targeted mutants in the Notch pathway have suggested a critical role for Notch signaling in vasculogenesis and angiogenesis. However, the angiogenic signaling that controls Notch and ligand gene expression is unknown. We show here that vascular endothelial growth factor (VEGF) but not basic fibroblast growth factor can induce gene expression of Notch1 and its ligand, Delta-like 4 (Dll4), in human arterial endothelial cells. The VEGF-induced specific signaling is mediated through VEGF receptors 1 and 2 and is transmitted via the phosphatidylinositol 3-kinase/Akt pathway but is independent of mitogen-activated protein kinase and Src tyrosine kinase. Constitutive activation of Notch signaling stabilizes network formation of endothelial cells on Matrigel and enhances formation of vessel-like structures in a three-dimensional angiogenesis model, whereas blocking Notch signaling can partially inhibit network formation. This study provides the first evidence for regulation of Notch/Delta gene expression by an angiogenic growth factor and insight into the critical role of Notch signaling in arteriogenesis and angiogenesis.

scholarly journals Differential non-target-derived repulsive signals play a critical role in shaping initial axonal growth of dorsal root ganglion neurons

2003 ◽  
Vol 254 (2) ◽  
pp. 289-302 ◽  
Author(s):  
Tomoyuki Masuda ◽  
Hiroshi Tsuji ◽  
Masahiko Taniguchi ◽  
Takeshi Yagi ◽  
Marc Tessier-Lavigne ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Critical Role ◽  
Axonal Growth ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

Shape Memory Polymers: A Potential Material for Future’s Changing Shape

2010 ◽  
Author(s):  
Jinsong Leng ◽  
Yanju Liu ◽  
Shanyi Du
Keyword(s):  
Shape Memory ◽  
Smart Materials ◽  
Low Cost ◽  
Critical Role ◽  
Shape Memory Polymers ◽  
Future Research ◽  
Comprehensive Review ◽  
Good Shape ◽  
Fundamental Understanding ◽  
Macroscopic Deformation

Shape memory polymers (SMPs) undergo significant macroscopic deformation upon the application of an external stimulus. As a novel and promising kind of smart materials, they have been widely researched since the 1980s. SMPs present many potential technical advantages that surpass those of shape memory alloys and shape memory ceramics such as good shape recoverability, low density, ease in processing and in tailoring of properties (e.g., transition temperature, stiffness, bio-degradability, and ease of functionally grading), programmability and controllability of recovery behavior, and most importantly, low cost. This paper aims to provide a comprehensive review of SMPs, encompassing a fundamental understanding of the shape memory of SMPs. The synthesis of SMPs is presented firstly. In order to realize the actuation of SMPs for a special application, the investigation of actuations in multi ways are performed, namely electroactive SMPs, light-responsive SMPs, magnetism-induced SMPs, and chemo-responsive SMPs. These novel actuation approaches play a critical role in the development of multifunctional materials that not only exhibit the shape memory effect but also perform particular functions. Based on the unique properties of such materials, primary applications are also listed, and the potential directions and applications of SMPs are proposed to be developed in future research.

scholarly journals Fiber Crimp Confers Matrix Mechanical Nonlinearity, Regulates Endothelial Cell Mechanosensing, and Promotes Microvascular Network Formation

2020 ◽  
Vol 142 (11) ◽  
Author(s):  
Christopher D. Davidson ◽  
Danica Kristen P. Jayco ◽  
William Y. Wang ◽  
Ariella Shikanov ◽  
Brendon M. Baker
Keyword(s):  
Type I Collagen ◽  
Network Formation ◽  
Critical Role ◽  
Type I ◽  
Matrix Remodeling ◽  
Simple Method ◽  
Nonlinear Stress ◽  
Nonlinear Mechanical ◽  
Hydrophilic Peptide ◽  
Fibrous Matrices

Abstract Mechanical interactions between cells and their surrounding extracellular matrix (ECM) guide many fundamental cell behaviors. Native connective tissue consists of highly organized, 3D networks of ECM fibers with complex, nonlinear mechanical properties. The most abundant stromal matrix component is fibrillar type I collagen, which often possesses a wavy, crimped morphology that confers strain- and load-dependent nonlinear mechanical behavior. Here, we established a new and simple method for engineering electrospun fibrous matrices composed of dextran vinyl sulfone (DexVS) with controllable crimped structure. A hydrophilic peptide was functionalized to DexVS matrices to trigger swelling of individual hydrogel fibers, resulting in crimped microstructure due to the fixed anchorage of fibers. Mechanical characterization of these matrices under tension confirmed orthogonal control over nonlinear stress–strain responses and matrix stiffness. We next examined ECM mechanosensing of individual endothelial cells (ECs) and found that fiber crimp promoted physical matrix remodeling alongside decreases in cell spreading, focal adhesion area, and nuclear localization of Yes-associated protein (YAP). These changes corresponded to an increase in migration speed, along with evidence for long-range interactions between neighboring cells in crimped matrices. Interestingly, when ECs were seeded at high density in crimped matrices, capillary-like networks rapidly assembled and contained tube-like cellular structures wrapped around bundles of synthetic matrix fibers due to increased physical reorganization of matrix fibers. Our work provides an additional level of mechanical and architectural tunability to synthetic fibrous matrices and implicates a critical role for mechanical nonlinearity in EC mechanosensing and network formation.

Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development

2017 ◽  
Vol 24 (2) ◽  
pp. 142-155 ◽  
Author(s):  
Jenna R. Gale ◽  
Armaz Aschrafi ◽  
Anthony E. Gioio ◽  
Barry B. Kaplan
Keyword(s):  
Neurodevelopmental Disorders ◽  
Growth And Development ◽  
Critical Role ◽  
Axonal Growth ◽  
Growth Cones ◽  
Heterogeneous Population ◽  
Clinical Implications ◽  
Nerve Terminals ◽  
Local Translation ◽  
Site Specific

Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

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