Damage biomechanics for neuronal membrane mechanoporation

Abstract

In this paper, mechano-physiological damage evolution equations are developed to capture the disruption of neuronal membrane integrity and quantify neuronal cell death in the brain during mechanical insult. Traumatic brain injury involves multiscale structure-property relations where the mechanical behavior of the brain is phenomenologically characterized at the macroscale. However, damage largely occurs at the cellular level (microscale and nanoscale) due to the loss of ion homeostasis. To measure this neuronal death mechanism, molecular dynamics simulations were performed on a representative neuronal membrane, a 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayer structures. Pore density and pore growth due to membrane deformation were then quantified. The results showed that the pore growth and pore density rates were a function of stress state, but only the pore growth rate was a function of the strain rate. Mechano-physiological damage evolution equations were developed to capture the damage biomechanics of the POPC bilayer based on the pore density and growth rate responses. The proposed damage evolution equations were combined with the Nernst-Planck diffusion Modelling and Simulation in Materials Science and Engineering

Coarse-Grained Modeling of Pore Dynamics on the Red Blood Cell Membrane under Large Deformations

“…Moreover, numerical simulations show that the stretching velocity of a patch at high shear rates, tank-treading motion, can reach to a few millimeters per second (5). However, the lowest stretching velocity in all-atomistic MD simulations is $100 mm/s (21,23,25), which results in unrealistically high critical strains. Considering the strain rate of 10 À5 t À1 , initial length of $420 nm, and time mapping of t z 10 ns, the stretching velocity in our model can be approximated as $0.42 mm/s, which is closer to the physiological range of shear-induced deformation velocities in medical devices under large deformations and high shear rate regimes (5).…”

“…During the last two decades, in silico molecular dynamics simulations have been widely used to study pores in biological membranes (18)(19)(20)(21)(22)(23)(24)(25)(26). AA simulations provide valuable insights into the free energy (18)(19)(20)22), critical areal strain (21), and underlying atomistic mechanisms of pore formation (18,19) and reseal (26).…”

Molecular dynamics simulations of phospholipid bilayer mechanoporation under different strain states—a comparison between GROMACS and LAMMPS

“…These events can induce irreversible cell membrane rupture and disrupt various cellular functions, ultimately causing cell death, tissue damage, and brain dysfunction at higher length scales [3,9]. Nonetheless, due to the mismatch in time and length scales, the relationship between the nanoscale physiological changes at cellular levels and the macroscale damages at organ levels are obscured [4,[10][11][12][13].…”

“…Several studies have been conducted in cell membrane deformation under mechanical stresses, as well as pore formation in phospholipid bilayer-the fundamental biological structure of cell membranes [4][5][6][7]. These studies utilize various approaches, both experimentally and computationally, to achieve a comprehensive understanding of the complex biomechanical cues behind mechano-physiological damages [4,7,12]. Several experiments have been performed on phospholipid bilayers to capture membrane behavior and rupture strength under stretching deformations, such as applying equibiaxial surface tension on the bilayer through micropipette aspiration [14,15], tracking biomarker during cell culture deformation [16,17], or investigating impulse-like stretching on red blood cells using laser-induced cavitation [18].…”

“…However, strain rate or strain state applied to the membrane, stress-strain response, and nanoscale mechanoporation (pore formation under mechanical loading) [6] are difficult to inspect in these meso-or micro-scale experiments [6,7]. Therefore, besides experimental studies, multiscale in silico models have been developed, aiming to scrutinize the damage dynamics, clarify mechanically plausible mechanisms, and establish injury threshold across different time and spatial resolutions [4][5][6][7][8][10][11][12][13]. Particularly, to elucidate nanoscale mechanoporation and damage evolution, the molecular dynamics (MD) simulation method has been utilized [5][6][7][19][20][21][22][23][24][25].…”