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Quantifying mechanical force in axonal growth and guidance.

Athamneh AI, Suter DM - Front Cell Neurosci (2015)

Bottom Line: In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections.Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics.We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

View Article: PubMed Central - PubMed

Affiliation: Bindley Bioscience Center, Birck Nanotechnology Center, Department of Biological Sciences, Purdue University West Lafayette, IN, USA.

ABSTRACT
Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight: (1) standing questions concerning the role of mechanical force in axonal growth and guidance; and (2) different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

No MeSH data available.


Related in: MedlinePlus

A simplified schematic of the cytoplasmic domains and cytoskeletal structures in the growth cone. Traction force is generated as a result of coupling of F-actin flow in the P domain to an extracellular adhesion substrate.
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Figure 1: A simplified schematic of the cytoplasmic domains and cytoskeletal structures in the growth cone. Traction force is generated as a result of coupling of F-actin flow in the P domain to an extracellular adhesion substrate.

Mentions: There is ample evidence that axonal elongation is influenced by both biochemical and biomechanical factors. The neuronal growth cone controls the direction and rate of axonal growth by navigating the surrounding environment searching for molecular, mechanical, and topographical cues. The machinery responsible for sensing stiffness of the extracellular matrix (ECM) as well as of neighboring cellular surfaces is primarily powered by the actin cytoskeleton, which is highly dynamic and is constantly turning over in the peripheral (P) domain and transition (T) zone (Figure 1). Actin polymerizes at the leading edge and is pulled backward by myosin motors, resulting in retrograde F-actin flow (Lin et al., 1996; Medeiros et al., 2006). Traction force is generated as a result of coupling of the F-actin flow to cellular and ECM substrates through adhesion receptors, such as immunoglobulin superfamily cell adhesion molecules, N-cadherin, and integrins (Suter et al., 1998; Bard et al., 2008; Shimada et al., 2008). Several reviews have discussed this substrate-cytoskeletal coupling model including what is known about the role of the cytoskeleton, molecular motors as well as signaling pathways involved (Suter and Forscher, 2000; Suter and Miller, 2011; Gomez and Letourneau, 2014).


Quantifying mechanical force in axonal growth and guidance.

Athamneh AI, Suter DM - Front Cell Neurosci (2015)

A simplified schematic of the cytoplasmic domains and cytoskeletal structures in the growth cone. Traction force is generated as a result of coupling of F-actin flow in the P domain to an extracellular adhesion substrate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4584967&req=5

Figure 1: A simplified schematic of the cytoplasmic domains and cytoskeletal structures in the growth cone. Traction force is generated as a result of coupling of F-actin flow in the P domain to an extracellular adhesion substrate.
Mentions: There is ample evidence that axonal elongation is influenced by both biochemical and biomechanical factors. The neuronal growth cone controls the direction and rate of axonal growth by navigating the surrounding environment searching for molecular, mechanical, and topographical cues. The machinery responsible for sensing stiffness of the extracellular matrix (ECM) as well as of neighboring cellular surfaces is primarily powered by the actin cytoskeleton, which is highly dynamic and is constantly turning over in the peripheral (P) domain and transition (T) zone (Figure 1). Actin polymerizes at the leading edge and is pulled backward by myosin motors, resulting in retrograde F-actin flow (Lin et al., 1996; Medeiros et al., 2006). Traction force is generated as a result of coupling of the F-actin flow to cellular and ECM substrates through adhesion receptors, such as immunoglobulin superfamily cell adhesion molecules, N-cadherin, and integrins (Suter et al., 1998; Bard et al., 2008; Shimada et al., 2008). Several reviews have discussed this substrate-cytoskeletal coupling model including what is known about the role of the cytoskeleton, molecular motors as well as signaling pathways involved (Suter and Forscher, 2000; Suter and Miller, 2011; Gomez and Letourneau, 2014).

Bottom Line: In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections.Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics.We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

View Article: PubMed Central - PubMed

Affiliation: Bindley Bioscience Center, Birck Nanotechnology Center, Department of Biological Sciences, Purdue University West Lafayette, IN, USA.

ABSTRACT
Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight: (1) standing questions concerning the role of mechanical force in axonal growth and guidance; and (2) different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

No MeSH data available.


Related in: MedlinePlus