Neuromechanics: The Role of Tension in Neuronal Growth and Memory

Ahmed, Wylie; Rajagopalan, Jagannathan; Tofangchi, Alireza; Saif, Taher A.

doi:10.1002/9781118482568.ch3

Cited by 7 publications

(8 citation statements)

References 81 publications

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“…A key feature of active motor crosslinking is that each crosslinks detaches at the contracted state and reattaches at its initial length, which generates active contraction and, on the axon level, an emergent rheology that is conceptually similar to an active force or internal stress [7, 10, 55]. The major molecularlevel parameters that govern these events are the average crosslink density and the characteristic detachment and reattachment time; the main axon-level parameters that emerge from these events are the stiffness and the viscosity.…”

Section: Discussionmentioning

confidence: 99%

“…Two more recent approaches suggest to interpret neurons as active fluids or solids [7,55,62] that are capable of generating active forces, conceptually similar to skeletal muscle [32, 37]. In both cases, internal forces generated at the expenditure of adenosine triphosphate, ATP, explain internal tensions at the steady state as proposed by active matter hydrodynamics [51].…”

Section: Introductionmentioning

confidence: 99%

“…However, it does not consider the elastic behavior of the axon, which limits its use to sufficiently long time spans of observation. The active solid model [7,10] and the morphoelastic rod model [52] excellently capture the elastic properties of axons. The morphoelastic rod model characterizes the behavior of axons over long periods of time using the theory of finite growth [62].…”

Section: Introductionmentioning

confidence: 99%

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Modeling molecular mechanisms in the axon

2016

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Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena–both in isolation and in interaction–to explore emergent cellular-level features under physiological and pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling molecular mechanisms in the axon

2016

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“…Mechanical tension in neurons has been implicated in the processes of growth, development, and signaling 24 25 26 . Normal vesicle transport plays critical roles in many different processes.…”

Section: Discussionmentioning

confidence: 99%

Active transport of vesicles in neurons is modulated by mechanical tension

Ahmed

Saif

2014

Sci Rep

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Effective intracellular transport of proteins and organelles is critical in cells, and is especially important for ensuring proper neuron functionality. In neurons, most proteins are synthesized in the cell body and must be transported through thin structures over long distances where normal diffusion is insufficient. Neurons transport subcellular cargo along axons and neurites through a stochastic interplay of active and passive transport. Mechanical tension is critical in maintaining proper function in neurons, but its role in transport is not well understood. To this end, we investigate the active and passive transport of vesicles in Aplysia neurons while changing neurite tension via applied strain, and quantify the resulting dynamics. We found that tension in neurons modulates active transport of vesicles by increasing the probability of active motion, effective diffusivity, and induces a retrograde bias. We show that mechanical tension modulates active transport processes in neurons and that external forces can couple to internal (subcellular) forces and change the overall transport dynamics.

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“…Computational simulations can provide powerful insights into the interplay of these different mechanisms and elucidate cause-effect relations that may be extremely difficult to obtain by experiments alone (25). Early models consider the axon as a one-dimensional viscoelastic structure that behaves as a solid at short timescales and as a fluid at longer timescales (26,27). These models accurately reproduce the axonal response in relaxation and creep experiments.…”

Section: Introductionmentioning

confidence: 99%

Microtubule Polymerization and Cross-Link Dynamics Explain Axonal Stiffness and Damage

Rooij

Kuhl

2018

Biophysical Journal

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Axonal damage is a critical indicator for traumatic effects of physical impact to the brain. However, the precise mechanisms of axonal damage are still unclear. Here, we establish a mechanistic and highly dynamic model of the axon to explore the evolution of damage in response to physical forces. Our axon model consists of a bundle of dynamically polymerizing and depolymerizing microtubules connected by dynamically detaching and reattaching cross-links. Although the probability of cross-link attachment depends exclusively on thermal fluctuations, the probability of detachment increases in the presence of physical forces. We systematically probe the landscape of axonal stretch and stretch rate and characterize the overall axonal force, stiffness, and damage as a direct result of the interplay between microtubule and cross-link dynamics. Our simulations reveal that slow loading is dominated by cross-link dynamics, a net reduction of cross-links, and a gradual accumulation of damage, whereas fast loading is dominated by cross-link deformations, a rapid increase in stretch, and an immediate risk of rupture. Microtubule polymerization and depolymerization decrease the overall axonal stiffness, but do not affect the evolution of damage at timescales relevant to axonal failure. Our study explains different failure mechanisms in the axon as emergent properties of microtubule polymerization, cross-link dynamics, and physical forces. We anticipate that our model will provide insight into causal relations by which molecular mechanisms determine the timeline and severity of axon damage after a physical impact to the brain.

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Neuromechanics: The Role of Tension in Neuronal Growth and Memory

Cited by 7 publications

References 81 publications

Modeling molecular mechanisms in the axon

Modeling molecular mechanisms in the axon

Active transport of vesicles in neurons is modulated by mechanical tension

Microtubule Polymerization and Cross-Link Dynamics Explain Axonal Stiffness and Damage

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