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Modeling molecular mechanisms in the axon

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Abstract

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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Acknowledgements

This study was supported by the Stanford Graduate Fellowship to Rijk de Rooij and by the Bio-X IIP seed Grant ‘Molecular Mechanisms of Chronic Traumatic Encephalopathy’ to Ellen Kuhl.

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Authors and Affiliations

  1. Departments of Mechanical Engineering and Bioengineering, Stanford University, Stanford, CA, 94305, USA

    R. de Rooij & E. Kuhl

  2. Department of Integrative Biology, Michigan State University, East Lansing, MI, 48824, USA

    K. E. Miller

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  1. R. de Rooij
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Correspondence to E. Kuhl.

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de Rooij, R., Miller, K.E. & Kuhl, E. Modeling molecular mechanisms in the axon. Comput Mech 59, 523–537 (2017). https://doi.org/10.1007/s00466-016-1359-y

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