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A model for stretch growth of neurons.

ABSTRACT: In the first phase of axon growth, axons sprout from neuron bodies and are extended by the pull of the migrating growth cones towards their targets. Thereafter, once the target is reached, a lesser known second phase of axon growth ensues as the mechanical forces from the growth of the animal induce extension of the integrated axons in the process of forming tracts and nerves. Although there are several microscopic physics based models of the first phase of axon growth, to date, there are no models of the very different second phase. Here we propose a mathematical model for stretch growth of axon tracts in which the rate of production of proteins required for growth is dependent on the membrane tension. We assume that growth occurs all along the axon, and are able to predict the increase in axon cross-sectional area after they are rapidly stretched and held at a constant length for several hours. We show that there is a length dependent maximum stretching rate that an axon can sustain without disconnection in steady state when the axon length is primarily increased near the cell body. Our results could inform better design of stretch growth protocols to create transplantable axon tracts to repair the nervous system.

SUBMITTER: Purohit PK

PROVIDER: S-EPMC8710257 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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A model for stretch growth of neurons.

Purohit Prashant K PK Smith Douglas H DH

Journal of biomechanics 20161118 16

In the first phase of axon growth, axons sprout from neuron bodies and are extended by the pull of the migrating growth cones towards their targets. Thereafter, once the target is reached, a lesser known second phase of axon growth ensues as the mechanical forces from the growth of the animal induce extension of the integrated axons in the process of forming tracts and nerves. Although there are several microscopic physics based models of the first phase of axon growth, to date, there are no mod ...[more]

PMID: 27890538

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Project description:Bio-engineered myocardium has great potential to substitute damaged myocardium and for studies of myocardial physiology and disease, but structural and functional immaturity still implies limitations. Current protocols of engineered heart tissue (EHT) generation fall short of simulating the conditions of postnatal myocardial growth, which are characterized by tissue expansion and increased mechanical load. To investigate whether these two parameters can improve EHT maturation, we developed a new approach for the generation of cardiac tissues based on biomimetic stimulation under application of continuously increasing stretch. Methods: EHTs were generated by assembling cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) at high cell density in a low collagen hydrogel. Maturation and growth of the EHTs were induced in a custom-made biomimetic tissue culture system that provided continuous electrical stimulation and medium agitation along with progressive stretch at four different increments. Tissues were characterized after a three week conditioning period. Results: The highest rate of stretch (S3 = 0.32 mm/day) increased force development by 5.1-fold compared to tissue with a fixed length, reaching contractility of 11.28 mN/mm². Importantly, intensely stretched EHTs developed physiological length-dependencies of active and passive forces (systolic/diastolic ratio = 9.47 ± 0.84), and a positive force-frequency relationship (1.25-fold contractility at 180 min-1). Functional markers of stretch-dependent maturation included enhanced and more rapid Ca2+ transients, higher amplitude and upstroke velocity of action potentials, and pronounced adrenergic responses. Stretch conditioned hiPSC-CMs displayed structural improvements in cellular volume, linear alignment, and sarcomere length (2.19 ± 0.1 µm), and an overall upregulation of genes that are specifically expressed in adult cardiomyocytes. Conclusions: With the intention to simulate postnatal heart development, we have established techniques of tissue assembly and biomimetic culture that avoid tissue shrinkage and yield muscle fibers with contractility and compliance approaching the properties of adult myocardium. This study demonstrates that cultivation under progressive stretch is a feasible way to induce growth and maturation of stem cell-derived myocardium. The novel tissue-engineering approach fulfills important requirements of disease modelling and therapeutic tissue replacement.

Dataset Information

A model for stretch growth of neurons.

Publications

A model for stretch growth of neurons.

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