Abstract
Neurons are mechanosensitive cells. The role of mechanical force in the process of neurite initiation, elongation and sprouting; nerve fasciculation; and neuron maturation continues to attract considerable interest among scientists. Force is an endogenous signal that stimulates all these processes in vivo. The axon is able to sense force, generate force and, ultimately, transduce the force in a signal for growth. This opens up fascinating scenarios. How are forces generated and sensed in vivo? Which molecular mechanisms are responsible for this mechanotransduction signal? Can we exploit exogenously applied forces to mimic and control this process? How can these extremely low forces be generated in vivo in a non-invasive manner? Can these methodologies for force generation be used in regenerative therapies? This review addresses these questions, providing a general overview of current knowledge on the applications of exogenous forces to manipulate axonal outgrowth, with a special focus on forces whose magnitude is similar to those generated in vivo. We also review the principal methodologies for applying these forces, providing new inspiration and insights into the potential of this approach for future regenerative therapies.
Highlights
Axonal elongation, guidance and navigation are crucial for the development of the nervous system
How are forces generated and sensed in vivo? Which molecular mechanisms are responsible for this mechanotransduction signal? Can we exploit exogenously applied forces to mimic and control this process? How can these extremely low forces be generated in vivo in a non-invasive manner? Can these methodologies for force generation be used in regenerative therapies? This review addresses these questions, providing a general overview of current knowledge on the applications of exogenous forces to manipulate axonal outgrowth, with a special focus on forces whose magnitude is similar to those generated in vivo
We reveal how exogenous mechanical forces act on axons, possibly resulting in the activation of pathways that influence every step of neuron development, from neurogenesis to synaptogenesis
Summary
Guidance and navigation are crucial for the development of the nervous system They require motion, and Newton’s laws states that motion is caused by forces. One reason why the therapeutic potential of force as a regulator of axonal outgrowth has been neglected for decades is the lack of methodologies to translate research outcomes into clinical research/practice. We intend to provide an overview of the various methods to manipulate axon outgrowth via exogenous forces, showing the ability to modulate every phase of neuronal growth and highlighting any future therapeutic applications. We review the methodologies for force application in terms of their therapeutic potential to stimulate axonal outgrowth in regeneration therapies
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