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

Clara L Essmann; Muna Elmi; Christoforos Rekatsinas; Nikolaos Chrysochoidis; Michael Shaw; Vijay Pawar; Mandayam A Srinivasan; Vasileios Vavourakis

doi:10.3389/fbioe.2024.1335788

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

Front Bioeng Biotechnol. 2024 Mar 15:12:1335788. doi: 10.3389/fbioe.2024.1335788. eCollection 2024.

Authors

Clara L Essmann^#^{1

2}, Muna Elmi^#², Christoforos Rekatsinas^#³, Nikolaos Chrysochoidis⁴, Michael Shaw^{2

5}, Vijay Pawar², Mandayam A Srinivasan², Vasileios Vavourakis^{6

7}

Affiliations

¹ Department of Bioinformatics and Molecular Genetics, University of Freiburg, Freiburg, Baden-Wuerttemberg, Germany.
² Department of Computer Science, University College London, London, United Kingdom.
³ Software and Knowledge Engineering Lab, Athens, Greece.
⁴ Department of Mechanical Engineering and Aeronautics, University of Patras, Patras, Greece.
⁵ National Physical Laboratory, Teddington, United Kingdom.
⁶ Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
⁷ Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.

^# Contributed equally.

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.

Keywords: Caenorhabditis elegans; aldicarb; atomic force microscopy; biomechanics; finite element method; optogenetics; osmotic shock.

Associated data

figshare/10.6084/m9.figshare.25303960

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Worm strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This project was partly funded by a European Research Council Advanced Grant (MicroNanoTeleHaptics; ID: 247041), a Engineering and Physical Sciences Research Council Grant (Robotic Teleoperation for Multiple Scales: Enabling Exploration, Manipulation and Assembly Tasks in New Worlds; ID: EP/K005030/1). MS was supported by the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS; ID: 203145Z/16/Z).