The purpose of this study is to conduct modeling and simulation to understand the effect of shock-induced mechanical loading, in the form of cavitation bubble collapse, on damage to the brain’s perineuronal nets (PNNs). It is known that high-energy implosion due to cavitation collapse is responsible for corrosion or surface damage in many mechanical devices. In this case, cavitation refers to the bubble created by pressure drop. The presence of a similar damage mechanism in biophysical systems has long being suspected but not well-explored. In this paper, we use reactive molecular dynamics (MD) to simulate the scenario of a shock wave induced cavitation collapse within the perineuronal net (PNN), which is the near-neuron domain of a brain’s extracellular matrix (ECM). Our model is focused on the damage in hyaluronan (HA), which is the main structural component of PNN. We have investigated the roles of cavitation bubble location, shockwave intensity and the size of a cavitation bubble on the structural evolution of PNN. Simulation results show that the localized supersonic water hammer created by an asymmetrical bubble collapse may break the hyaluronan. As such, the current study advances current knowledge and understanding of the connection between PNN damage and neurodegenerative disorders.

As a major cytoskeleton element of the axon, the breaking of microtubules (MTs) has been considered as a major cause of the axon degeneration. High strain rate loading is considered as one of the key factors in microtubule breaking. Due to the small size of microtubule, the real-time behavior of microtubule breaking is hard to capture. This study employs fully-atomistic molecular dynamics (MD) simulation to determine the failure modes of microtubule under different loadings conditions such as, unidirectional stretching, bending and hydrostatic expansion. For each loading conditions, MT is subjected to extreme high strain rate (10⁸–10⁹ s⁻¹) loading. We argue that such level of high strain rate may be realized during cavitation bubble implosion. For each loading type, we have determined the critical energy for MT rupture. The associated rupture mechanisms are also discussed. We observed that the stretching has the lowest energy barrier to break the MT at the nanosecond time scale. Moreover, the breakage between the dimers starts at ~16% of total strain when stretched, which is much smaller compared to the reported strain-at-failure (50%) for lower strain rate loading. It suggests that MT fails at a significantly smaller strain states when loaded at higher strain rates.

We have studied the molecular level cavitation mechanisms and bubble growth kinetics in soft gelatin hydrogel and water. The apparent difference in cavitation threshold pressure between that generates in pure water and that in gelatin hydrogel is considered. Gelatin, which is derived from collagen, is frequently used as a brain simulant material. In liquid, cavitation bubble is created when surrounding pressure drops below the saturation vapor pressure. In principle, a cavitation bubble should continue to grow as long as tensile pressure continues to increase in the system. In our study, using molecular dynamics simulation, we have investigated the pressure requirement for a nanoscale cavitation to grow in water and gel. First, we have modeled a gel like structure with a preexisting bubble of 5 nm radius. A control model containing a 5 nm bubble in pure water is also created. Then, we have applied hydrostatic tensile pressure at two different expansion rates in the gel and water models. The results show that a gel-like structure requires higher pressure for the cavitation to grow, and both gel and water models exhibit strain rate effect on the cavitation threshold pressure. We have also found that the cavitation collapse time is dominated by the viscosity of the medium.

• Actin: Strain rate and length dependent failure or stretching. • Spectrin: Strain rate dependent unfolding of inter-repeat regions. • Actin-Spectrin Network: strain rate dependent vulnerable regions are actin-spectrin interface or spectrin interrepeats.