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The influence of internal pressure and neuromuscular agents on C. elegans biomechanics: an empirical and multi-compartmental in silico modelling study
Frontiers in Bioengineering and Biotechnology ( IF 5.7 ) Pub Date : 2024-03-15 , DOI: 10.3389/fbioe.2024.1335788
Clara L. Essmann , Muna Elmi , Christoforos Rekatsinas , Nikolaos Chrysochoidis , Michael Shaw , Vijay Pawar , Mandayam A. Srinivasan , Vasileios Vavourakis

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.

中文翻译:

内部压力和神经肌肉药物对线虫生物力学的影响:实证和多室硅模型研究

特定组织的功能及其生物力学是相互依赖的,病理或衰老常常与结构衰退交织在一起。的生物力学秀丽隐杆线虫是一种广泛应用于药理学和衰老研究的模式生物,已被确立为健康衰老的生物标志物。然而,组成组织的特性及其对生物体整体机械特性的贡献仍然相对未知。在这项研究中,我们研究了健康人的生物力学线虫结合压痕实验和计算机模拟造型。我们使用原子力显微镜进行刚度测量。为了近似线虫的圆柱体,我们使用了一种新颖的三室非线性有限元模型,使我们能够分析各个室的弹性变化如何影响体积刚度。然后,我们微调模型的参数,以使模拟力压痕输出与实验数据相匹配。为了测试有限元模型,我们通过实验修改了不同的隔间。我们的计算机模拟结果与之前的研究一致,表明高渗休克通过降低内部压力来降低刚度。出乎意料的是,传统上与​​肌肉收缩相关的神经肌肉药物涕灭威治疗通过降低内部压力来减少僵硬。此外,我们的有限元模型可以深入了解药物、突变或衰老等过程如何针对个体组织。
更新日期:2024-03-15
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