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

The function of a specific tissue and its biomechanics are interdepended, with pathologies or ageing often being intertwined with structural decline. The biomechanics of Caenorhabditis elegans (C. elegans), a model organism widely used in pharmacological and ageing research, has been established as biomarker for healthy ageing, though the mechanics of individual tissues have remained elusive. 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. Nematode stiffness measurements were performed using an atomic force microscope. The worms cylindrical body was approximated using a novel three-compartmental nonlinear finite element model, enabling analysis of how changes in the elasticity of individual compartments affect the bulk stiffness of C. elegans. The parameters of the model were then fine-tuned to match the simulation force-indentation output to the experimental data. To test the finite element model, distinct compartments were modified experimentally. Our in silico results, in agreement with previous studies, suggest that hyperosmotic shock reduced stiffness by decreasing the C. elegans internal pressure. Unexpectedly, treatment with the neuromuscular agent aldicarb, traditionally associated with muscle contraction, reduced stiffness by decreasing the internal pressure. It challenges previous assumptions about the effects of aldicarb. Furthermore, our finite element model can offer insights into how drugs, mutations or processes like ageing target individual tissues.