The influence of internal pressure and neuromuscular agents on C. elegans biomechanics: an empirical and multi-compartmental in silico modelling study

内部压力和神经肌肉剂对秀丽隐杆线虫生物力学的影响:一项实证和多室计算机建模研究

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作者:Clara L Essmann #, Muna Elmi #, Christoforos Rekatsinas #, Nikolaos Chrysochoidis, Michael Shaw, Vijay Pawar, Mandayam A Srinivasan, Vasileios Vavourakis

Abstract

The function of a specific tissue and its biomechanics are interdependent, with pathologies or ageing often being intertwined with structural decline. The biomechanics of Caenorhabditis elegans, a model organism widely used in pharmacological and ageing research, has been established as biomarker for healthy ageing. However, the properties of the constituent tissues, and their contribution to the overall mechanical characteristics of the organism, remain relatively unknown. In this study we investigated the biomechanics of healthy C. elegans cuticle, muscle tissue, and pseudocoelom using a combination of indentation experiments and in silico modelling. We performed stiffness measurements using an atomic force microscope. To approximate the nematode's cylindrical body we used a novel three-compartment nonlinear finite element model, enabling us to analyse of how changes in the elasticity of individual compartments affect the bulk stiffness. We then fine-tuned the parameters of the model to match the simulation force-indentation output to the experimental data. To test the finite element model, we modified distinct compartments experimentally. Our in silico results, in agreement with previous studies, suggest that hyperosmotic shock reduces stiffness by decreasing the internal pressure. Unexpectedly, treatment with the neuromuscular agent aldicarb, traditionally associated with muscle contraction, reduced stiffness by decreasing the internal pressure. Furthermore, our finite element model can offer insights into how drugs, mutations, or processes such as ageing target individual tissues.

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