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The mechanical effects of chemical stimuli on neurospheres

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Abstract

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of the CCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

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Acknowledgements

This work was supported through funding from the Canada Foundation for Innovation and the Engage and Discovery Grants Program of the Natural Sciences and Engineering Research Council of Canada. The cantilevered-capillary force apparatus (CCFA) was designed and fabricated by John M. Frostad through funding from the Canada Foundation for Innovation.

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Yun-Han Huang contributed to formal analysis, investigation, data Curation, writing—original draft, writing—review and editing, visualization. Roza Vaez Ghaemi contributed to conceptualization, methodology, software, validation, formal analysis, investigation, data curation, writing—original draft, writing—review and editing, visualization. James Cheon contributed to formal analysis, investigation, data curation, writing—original draft, visualization. Vikramaditya G. Yadav contributed to conceptualization, methodology, formal analysis, resources, writing—original draft, writing—review and editing, supervision, project administration, funding acquisition. John M. Frostad contributed to conceptualization, methodology, formal analysis, resources, writing—original draft, writing—review and editing, supervision, project administration, funding acquisition.

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Correspondence to Vikramaditya G. Yadav or John M. Frostad.

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Huang, YH., Vaez Ghaemi, R., Cheon, J. et al. The mechanical effects of chemical stimuli on neurospheres. Biomech Model Mechanobiol (2024). https://doi.org/10.1007/s10237-024-01841-7

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