Measurement of Subcellular Force Generation in Neurons

O'Toole, Matthew R.; Lamoureux, Phillip; Miller, Kyle E.

doi:10.1016/j.bpj.2015.01.021

Cited by 52 publications

(100 citation statements)

References 71 publications

(137 reference statements)

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“…Although we observed traction forces in the 10 0 to 10 1 nN range similar to previous studies (19,20,29,31), we are the first, to our knowledge, to report growth cone forces up in the 10 2 nN range. Considering the large size and cytoskeletal mass of Aplysia growth cones such high force levels may not be surprising.…”

Section: Traction Force Gradually Increases During Adhesion-mediated supporting

confidence: 74%

“…In both approaches, the probe (a bead attached to the AFM cantilever tip or the microneedle tip) was brought into contact with the dorsal side of the growth cone P domain and kept in place allowing the growth cone to pull on the force-sensing device. Unlike previous studies using microneedles where external forces were applied on growth cones and axons (4,8,29), in our experiment no towing or any other external force was applied. Fig.…”

Section: Quantifying Traction Force Generation In Growth Cones Encounmentioning

confidence: 78%

“…Saif and co-worker (6,36) fabricated a silicon-based micromechanical force sensor to measure rest tension in the axons of Drosophila neurons in vivo and found it to be in the 10 0 to 10 1 nN range. Recently, O'Toole et al (29) presented a mathematical model describing the relationship between subcellular forces arranged in series within the axon and the net axonal tension. They elegantly combined the use of force-calibrated microneedle to measure and apply force with labeling of docked mitochondria to monitor subcellular strain in chick sensory neurons.…”

Section: Quantification Of Traction Force Generation During Adhesion-mentioning

confidence: 99%

“…Force-calibrated microneedles were employed in the earliest quantitative work and provided a global view of mechanical force at the whole neuron and neurite level, but the details of force generation and distribution at the growth cone level remained unclear (4,5,8,(27)(28)(29)37,38). Traction force microscopy enabled quantitative force measurements at the growth cone level and presented high-resolution visualization of force distribution in the growth cone (18)(19)(20)23).…”

Section: Introductionmentioning

confidence: 99%

“…Different experimental methodologies have been utilized to quantify forces in axons and growth cones including the use of 1) force-calibrated microneedles (3,4,9,(27)(28)(29), 2) traction force microscopy on flexible substrates (11,14,(18)(19)(20)23,30) or fabricated nanowire arrays (31), 3) optical tweezers (16,(32)(33)(34), 4) atomic force microscope (AFM) (35), and 5) microfabricated silicon-based micromechanical force sensors (6,36). Force-calibrated microneedles were employed in the earliest quantitative work and provided a global view of mechanical force at the whole neuron and neurite level, but the details of force generation and distribution at the growth cone level remained unclear (4,5,8,(27)(28)(29)37,38).…”

Section: Introductionmentioning

confidence: 99%

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Substrate Deformation Predicts Neuronal Growth Cone Advance

Athamneh

Cartagena‐Rivera

Raman

et al. 2015

Biophysical Journal

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Although pulling forces have been observed in axonal growth for several decades, their underlying mechanisms, absolute magnitudes, and exact roles are not well understood. In this study, using two different experimental approaches, we quantified retrograde traction force in Aplysia californica neuronal growth cones as they develop over time in response to a new adhesion substrate. In the first approach, we developed a novel method, to our knowledge, for measuring traction forces using an atomic force microscope (AFM) with a cantilever that was modified with an Aplysia cell adhesion molecule (apCAM)-coated microbead. In the second approach, we used force-calibrated glass microneedles coated with apCAM ligands to guide growth cone advance. The traction force exerted by the growth cone was measured by monitoring the microneedle deflection using an optical microscope. Both approaches showed that Aplysia growth cones can develop traction forces in the 10 0 -10 2 nN range during adhesion-mediated advance. Moreover, our results suggest that the level of traction force is directly correlated to the stiffness of the microneedle, which is consistent with a reinforcement mechanism previously observed in other cell types. Interestingly, the absolute level of traction force did not correlate with growth cone advance toward the adhesion site, but the amount of microneedle deflection did. In cases of adhesion-mediated growth cone advance, the mean needle deflection was 1.05 5 0.07 mm. By contrast, the mean deflection was significantly lower (0.48 5 0.06 mm) when the growth cones did not advance. Our data support a hypothesis that adhesion complexes, which can undergo micron-scale elastic deformation, regulate the coupling between the retrogradely flowing actin cytoskeleton and apCAM substrates, stimulating growth cone advance if sufficiently abundant.

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Section: Traction Force Gradually Increases During Adhesion-mediated supporting

confidence: 74%

Section: Quantifying Traction Force Generation In Growth Cones Encounmentioning

confidence: 78%

Section: Quantification Of Traction Force Generation During Adhesion-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Substrate Deformation Predicts Neuronal Growth Cone Advance

Athamneh

Cartagena‐Rivera

Raman

et al. 2015

Biophysical Journal

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Neuromechanobiology: An Expanding Field Driven by the Force of Greater Focus

Motz

Kabat

Saxena

et al. 2021

Adv Healthcare Materials

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The brain processes information by transmitting signals through highly connected and dynamic networks of neurons. Neurons use specific cellular structures, including axons, dendrites and synapses, and specific molecules, including cell adhesion molecules, ion channels and chemical receptors to form, maintain and communicate among cells in the networks. These cellular and molecular processes take place in environments rich of mechanical cues, thus offering ample opportunities for mechanical regulation of neural development and function. Recent studies have suggested the importance of mechanical cues and their potential regulatory roles in the development and maintenance of these neuronal structures. Also suggested are the importance of mechanical cues and their potential regulatory roles in the interaction and function of molecules mediating the interneuronal communications. In this review, the current understanding is integrated and promising future directions of neuromechanobiology are suggested at the cellular and molecular levels. Several neuronal processes where mechanics likely plays a role are examined and how forces affect ligand binding, conformational change, and signal induction of molecules key to these neuronal processes are indicated, especially at the synapse. The disease relevance of neuromechanobiology as well as therapies and engineering solutions to neurological disorders stemmed from this emergent field of study are also discussed.

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Lang¹,

Waters²,

Vella³

et al. 2018

Multiscale Soft Tissue Mechanics and Mechanobiology

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Diffuse brain injury is caused by rapid rotation of the head, and causes strain injury to tissue throughout the brain. Following strain injury axons exhibit delayed recovery, showing regional buckling behavior immediately after stretch and returning to their original appearance over an extended period of time. This axonal buckling is hypothesized to occur as a result of localized stretching within the axon: Rapid strain causes mechanical damage to microtubules, increasing the effective length of axons. This damage is repaired gradually returning the axon to its initial length.Here, we test the hypothesis that localized stretching is a possible explanation for the regional buckling behavior. An elongated region of axon is modeled as an Euler beam on an elastic foundation, where the foundation represents the surrounding brain tissue, which consists of glial cells and extracellular matrix. After stretch the elastic foundation returns immediately to its pre-stretch length, while the axon is initially elongated and returns to its original length over a longer period of time. The model exhibits solutions similar to those observed experimentally in post-stretch axons, with undulations that have a similar wavelength and amplitude.

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Measurement of Subcellular Force Generation in Neurons

Cited by 52 publications

References 71 publications

Substrate Deformation Predicts Neuronal Growth Cone Advance

Substrate Deformation Predicts Neuronal Growth Cone Advance

Neuromechanobiology: An Expanding Field Driven by the Force of Greater Focus

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