Neuron dynamics on directional surfaces

Basso, Joao; Yurchenko, Ilya; Wiens, Matthew R; Staii, Cristian

doi:10.1039/c9sm01769k

Cited by 9 publications

(14 citation statements)

References 44 publications

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“…Treatment of neural cells with blebbistatin results in extensive outgrowth of neurites as a consequence of abolished retrograde actin flow, when the balance of extension and retraction of cell protrusion is shifted to extension. Several studies employed blebbistatin to demonstrate the role of actomyosin contractility using primary neurons from mice (Kollins et al, 2009;Hur et al, 2011;Yu et al, 2012;Dupraz et al, 2019;, rats (Allingham et al, 2005;Kubo et al, 2008;Kollins et al, 2009;Pool et al, 2011;Roland et al, 2014;Spedden et al, 2014;Evans et al, 2017;Wang et al, 2017Wang et al, , 2020Tanaka et al, 2018;Basso et al, 2019;, chickens (Rosner et al, 2007;Kollins et al, 2009;Xie et al, 2014), or even gastropods, such as Aplysia (Medeiros et al, 2006) and Helisoma trivolvis (Tornieri et al, 2006). These studies were performed in non-human primary neural cells, and investigated the neurite growth in matured neurons.…”

Section: Discussionmentioning

confidence: 99%

“…A major determinant of the reduced neuronal regeneration is the diminished axonal growth capacity of mature neurons. Extensive studies have been performed to elucidate the process of axonal growth impairment (Allingham et al, 2005;Medeiros et al, 2006;Tornieri et al, 2006;Rosner et al, 2007;Kubo et al, 2008;Kollins et al, 2009;Hur et al, 2011;Pool et al, 2011;Yu et al, 2012;Roland et al, 2014;Spedden et al, 2014;Xie et al, 2014;Evans et al, 2017;Wang et al, 2017Wang et al, , 2020Tanaka et al, 2018;Basso et al, 2019;Dupraz et al, 2019;, and, in addition to the intrinsic factors, revealed the importance of environmental inhibitory mechanisms in retarded axonal growth (Ichikawa et al, 2009;Hur et al, 2011;Tan et al, 2011;Beller and Snow, 2014;Baldwin and Giger, 2015;Nakamura et al, 2019). Because of the limited availability of human neural tissues, most of these studies used rodent or avian models.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II

Lilienberg

Hegyi

Szabó

et al. 2021

Front. Cell Dev. Biol.

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Studies on neural development and neuronal regeneration after injury are mainly based on animal models. The establishment of pluripotent stem cell (PSC) technology, however, opened new perspectives for better understanding these processes in human models by providing unlimited cell source for hard-to-obtain human tissues. Here, we aimed at identifying the molecular factors that confine and modulate an early step of neural regeneration, the formation of neurites in human neural progenitor cells (NPCs). Enhanced green fluorescent protein (eGFP) was stably expressed in NPCs differentiated from human embryonic and induced PSC lines, and the neurite outgrowth was investigated under normal and injury-related conditions using a high-content screening system. We found that inhibitors of the non-muscle myosin II (NMII), blebbistatin and its novel, non-toxic derivatives, initiated extensive neurite outgrowth in human NPCs. The extracellular matrix components strongly influenced the rate of neurite formation but NMII inhibitors were able to override the inhibitory effect of a restrictive environment. Non-additive stimulatory effect on neurite generation was also detected by the inhibition of Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1), the upstream regulator of NMII. In contrast, inhibition of c-Jun N-terminal kinases (JNKs) had only a negligible effect, suggesting that the ROCK1 signal is dominantly manifested by actomyosin activity. In addition to providing a reliable cell-based in vitro model for identifying intrinsic mechanisms and environmental factors responsible for impeded axonal regeneration in humans, our results demonstrate that NMII and ROCK1 are important pharmacological targets for the augmentation of neural regeneration at the progenitor level. These studies may open novel perspectives for development of more effective pharmacological treatments and cell therapies for various neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II

Lilienberg

Hegyi

Szabó

et al. 2021

Front. Cell Dev. Biol.

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“…Each surface is characterized by a different value of the pattern spatial period d , defined as the distance between two neighboring ridges ( Figure 1 a). To make these periodic patterns, we used a simple fabrication method based on imprinting diffraction grids with different grating constants onto PDMS substrates ( Supplementary Materials and [ 33 ]). The direction of the pattern is shown in Figure 1 by the parallel bright stripes (ridges) and by the parallel dark stripes (troughs).…”

Section: Methodsmentioning

confidence: 99%

“…All neuronal cells have been imaged using fluorescence microscopy (a total of 18 images). Fluorescence images were acquired using a standard Fluorescein isothiocyanate -FITC filter: excitation: 495 nm and emission: 521 nm (details on acquiring the fluorescence images are provided in the Supplementary Materials and [ 33 ]). For the experiments on chemically modified cells, we have treated the neurons with either: (1) Taxol (10 μM concentration) or (2) the chemical compound Y-27632 (10 μM concentration), which have been added to the neuron growth medium at the time of plating ( Supplementary Materials ).…”

Section: Methodsmentioning

confidence: 99%

Neuronal Growth and Formation of Neuron Networks on Directional Surfaces

et al. 2021

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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.

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“…While these works discuss mechanisms and constraints at play in chemotaxis or mechanical guidance, they do not seek to describe the path of the growth cone as a response to these stimuli. To that end, trajectories of growth cones seen as a random motion on a 2D substrate have been studied by multiple authors (Katz et al 1984;Mortimer et al 2010;Maskery et al 2004;Van Ooyen 1999, 2000;Krottje and Van Ooyen 2007;Borisyuk et al 2008;Buettner et al 1994;Wang et al 2003;Pearson et al 2011;Ben-Jacob 2000, 2001;Basso et al 2019;Yurchenko et al 2019Yurchenko et al , 2021Davis et al 2017;Roberts et al 2014); see also the review by Maskery and Shinbrot (2005). The main focus in these works is not the mechanism of elongation, as treated before, but rather the shape and statistical properties of growth cone trajectories, as a function of external cues.…”

Section: Guidancementioning

confidence: 99%

Mathematical models of neuronal growth

Oliveri

Goriely

2022

Biomech Model Mechanobiol

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The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites—axons and dendrites—to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.

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Neuron dynamics on directional surfaces

Abstract: We quantify neuronal growth on substrates with controlled geometries and present a theoretical approach that describes the motion of axons.

Cited by 9 publications

References 44 publications

Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II

Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-muscle Myosin II

Neuronal Growth and Formation of Neuron Networks on Directional Surfaces

Mathematical models of neuronal growth

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