Year: 2026
Type: article
Abstract: Actin filaments are found in abundance in the neuron cytoskeleton, cell body, and dendrites. In the context of multiscale traumatic brain injury (TBI) analysis, in which a single mechanical impact can trigger damage ranging from molecular and subcellular disruptions to cellular and tissue-level structural changes, understanding the damage thresholds and failure mechanisms of actin filaments in response to mechanical trauma is essential. Structurally, actin filaments are comprised of polymerized globular actin (G-actin) and play a pivotal role in maintaining the structural integrity and functional properties of neurons. The dynamic nature of actin filaments, including their polymerization and depolymerization, enables them to respond rapidly to changes in mechanical stress and cellular signaling. However, this adaptability also makes actin filaments vulnerable to mechanical injury, especially in the event of TBI. Although there are a few isolated studies on the mechanical response of actin filaments, a systematic study of the failure strain threshold under mechanical loading remains unexplored. Nevertheless, modeling the overall failure analysis of neurons requires a reliable estimate of this value. This study primarily aims to evaluate the mechanical damage of actin filaments using Molecular Dynamics (MD) simulations. Using MD simulations, this research has reported the primary value of failure strain for actin filaments under varying high-strain-rate mechanical loadings 10 7 , 10 8 and, 10 9 S −1 . Here, failure refers to the structural rupture of the actin filament. The molecular simulations were conducted using LAMMPS, the widely accessible molecular dynamics solver. The interatomic potentials for the interacting atoms and molecules were modeled using OPLS force fields. Standard simulation steps, including energy minimization, equilibration, and uniaxial tensile stretching, have been followed. Here, we find that failure of actin filaments predominantly initiates at strains of approximately 5–8%, with visible structural rupture occurring at around 12–14% strain. Along with that, the failure strain for actin filaments at different higher temperatures is also quantified. The findings regarding that failure strain are analogous to those reported in other research. This provides a reasonable validation for the simulation findings and the proposed atomistic theoretical explanation. Extending this analysis to dendrites and the cell body provides a more comprehensive understanding of how neuronal injury occurs and propagates across different subcellular regions of the neuron, with significant implications for injury risk prediction in TBI. Ultimately, the findings from this study are expected to contribute to the development of a more holistic model of neuronal injury.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,090
Funder: Office of Naval Research
Awards: G3768722492, G8876996369
OpenAlex ID: W7208836571