Molecular dynamics of complex neuronal cell membrane deformation and failure under different traumatic brain injury scenarios

Abstract

Neuronal membrane mechanical deformation and disruption are nanoscale damage mechanisms that critically affect brain cell function and viability during traumatic brain injury (TBI). The nanoscale cellular impairments are elusive in experiments and necessitate computational approaches such as molecular dynamics (MD) simulations. Implementing MD simulations, the current study investigates the mechanical deformation, failure, and mechanoporation damage of complex neuronal membrane systems under different strain rates and strain states in the context of TBI. The obtained results revealed that lower strain rates and more equibiaxial strain states were more detrimental to the neuronal membrane, leading to lower failure strain and higher damage during the mechanoporation process. Lower strain rates resulted in fewer pores with larger sizes, as well as smaller strain and area per lipid at failure. Meanwhile, more equibiaxial strain states exhibited more pores and larger pores, thus higher damage and lower failure strain. Regardless of the strain states it was subjected to, the membrane failed when reaching a critical area per lipid value. Moreover, the Membrane Failure Limit Diagram (MFLD) was updated for a complex multicomponent membrane model to identify the strain limits for potential neuronal membrane failure, aiding in the prediction of TBI-related phenomena. Overall, the study provides a non-invasive approach that progresses the current understanding of neuronal mechanical behavior and damage dynamics under various TBI scenarios, and lays the foundation for future biomedical research in brain injury biomechanics.