Impact of Shock-Induced Cavitation Bubble Collapse on the Damage of Cell Membranes with Different Lipid Peroxidation Levels

Abstract

Although the interaction mechanism between shock waves and cells is critical for advancing the medical applications of shock waves, we still have little understanding about it. This work aims to study the response of diseased cells subjected to lipid peroxidation to the nanojet from shock wave-induced bubble collapse by using the coarse-grained molecular dynamics simulation. Factors considered in the simulations include the shock velocity (u p), movement time of piston (τp), bubble size (R), and peroxidation level of membranes. Here, we mainly focus on the role of peroxidation levels, that is, the degree (%) and the distribution of oxidized lipids in membranes. The results indicate that the shock damage threshold (u p at which the pore in membranes is formed) of peroxidation membranes is less than that of normal membranes and decreases with the peroxidation degree. Importantly, the distribution of oxidized lipids has more effect on the damage threshold than the peroxidation degree. The threshold of membrane with 33% localized oxidized lipids is lower than that of membrane with 50% average oxidized lipids. The results can be explained by the stretching modulus (κs) and bending modulus (κb) of cell membranes. For example, the κb value (4.3 × 10–20 J) of 100% peroxidation membrane is about half of that (8.4 × 10–20 J) of a membrane without peroxidation. A lower modulus means high deformation under the same impact. Further analysis shows that peroxidation introduces a polar hydrophobic group to the tail of phospholipids that increases the hydrophilicity of tails and warps the tail of phospholipids toward the membrane–water interface, resulting in looser accumulation. This can be confirmed by the increased average phospholipid area with peroxidation levels. Indeed, most of the pores formed during the shock can heal. However, the permeation of water molecules across the healing membrane still increased. All these membrane-level information obtained from this study will be useful for improving the biomedical applications of shock waves.

Impact of Lipid Peroxidation on the Response of Cell Membranes to High-Speed Equibiaxial Stretching: A Computational Study

“…Moreover, from Table , we can see that both K A and γ L of the fully oxidized lipid bilayer (100 mol %), compared to those of the 0 mol % system, show a notable decrease. Our recent work also provided that the modulus of peroxidation bilayers was less than that of pure 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer. The change shows that the 100 mol % membrane model has a lower resistance to tensile loadings and damaging energy threshold.…”

Focal opening of the neuronal plasma membrane by shock-induced bubble collapse for drug delivery: a coarse-grained molecular dynamics simulation

“…19,20 For membranes, more studies have focused on the effects of shock waves and bubbles due to the use of one-component models. [21][22][23] Based on multi-component models, a small number of studies have revealed the influence of components such as cholesterol 24 or peroxidized phospholipid 25 on the response of membranes to shock. In fact, typical plasma membranes (PM) contain hundreds of different lipids.…”

How Shockwaves Open Tight Junctions of Blood–Brain Barrier: Comparison of Three Biomechanical Effects

“…If structural damage recovers slowly, it will evolve into more severe features such as pericyte detachment, astrocyte end-feet swelling or loss, and disrupted capillary basement membrane . Therefore, we perform the recovery simulation (100 ns) with the NPzAT ensemble as before . According to the analysis of helical content and RMSD (Figure S8), only compression damage (single shockwave) can recover in 100 ns.…”

“…11 Therefore, we perform the recovery simulation (100 ns) with the NPzAT ensemble as before. 18 According to the analysis of helical content and RMSD (Figure S8), only compression damage (single shockwave) can recover in 100 ns. Protein damage subjected to shock-induced cavitation does not recover appreciably within the limited MD simulation time.…”

“…Molecular dynamics (MD) simulations have developed into a powerful tool for providing detailed molecular pictures involved in biological processes, − based on the underlying models. Anatomically, the BBB is composed of endothelial cells, tight junctions (TJs) between endothelial cells, basement membrane, pericyte, and astrocyte end feet.…”