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

Cell permeabilization using shock-induced bubble collapse provides an attractive choice for drug delivery systems. In this work, based on a realistically human brain plasma membrane (PM) model, we investigated the focal opening of this complex model by the jet from cavitation, focusing on the effect of characteristic membrane components, particle velocity (u_p) and bubble diameters (D). Both high levels of cholesterol and specific cerebrosides in the PM model limit the pore opening of cavitation jets. Sphingomyelin is the opposite, but has little effect due to its low content. Two adjustable parameters of u_p and D can be coupled to control the opening size. The relationship between them and the maximum pore area was provided for the first time. The maximum pore area increases with the u_p (or the impulse that is positively related to u_p) in the low-speed range, which agrees with the experimentally observed impulse determinism. However, the maximum area drops in the high-speed range. Combined with D, we proposed that the jet size determines the pore size, not the impulse. Larger bubbles that can create a larger pore in the membrane have a larger jet size, but their impulse is relatively small. Finally, the recovery simulation shows that the membrane with a small pore can be quickly recovered within 300 ps, while that with a larger pore did not recover until 2 μs. These rules from this work may be helpful to optimize the choice of shock waves for the delivery of different drugs across membranes.