Department of Mechanical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Nanoscale. 2018 Mar 8;10(10):4761-4770. doi: 10.1039/c7nr08879e.
Therapeutic agent loaded micro and nanoscale particles as high-velocity projectiles can penetrate cells and tissues, thereby serving as gene and drug delivery vehicles for direct and rapid internalization. Despite recent progress in developing micro/nanoscale ballistic tools, the underlying biophysics of how fast projectiles deform and penetrate cell membranes is still poorly understood. To understand the rate and size-dependent penetration processes, we present coarse-grained molecular dynamics simulations of the ballistic impact of spherical projectiles on lipid membranes. Our simulations reveal that upon impact, the projectile can pursue one of three distinct pathways. At low velocities below the critical penetration velocity, projectiles rebound off the surface. At intermediate velocities, penetration occurs after the projectile deforms the membrane into a tubular thread. At very high velocities, rapid penetration occurs through localized membrane deformation without tubulation. Membrane tension, projectile velocity and size govern which phenomenon occurs, owing to their positive correlation with the reaction force generated between the projectile and the membrane during impact. Two critical membrane tension values dictate the boundaries among the three pathways for a given system, due to the rate dependence of the stress generated in the membrane. Our findings provide broad physical insights into the ballistic impact response of soft viscous membranes and guide design strategies for drug delivery through lipid membranes using micro/nanoscale ballistic tools.
载药的微纳米颗粒作为高速抛射体可以穿透细胞和组织，因此可作为基因和药物的输送载体，实现直接和快速内化。尽管在开发微/纳米级弹道工具方面取得了最近的进展，但对于抛射体如何快速变形和穿透细胞膜的基本生物物理特性仍了解甚少。为了理解速度和尺寸依赖性的穿透过程，我们对球形抛射体对脂质膜的弹道冲击进行了粗粒化分子动力学模拟。我们的模拟表明，在冲击时，抛射体可以遵循三种不同的途径之一。在低于临界穿透速度的低速度下，抛射体会从表面反弹。在中等速度下，在抛射体使膜变形为管状线后会发生穿透。在非常高的速度下，通过局部膜变形而无需成管即可快速穿透。由于抛射体和膜之间在冲击过程中产生的反作用力与膜张力、抛射体速度和尺寸呈正相关，因此这些因素决定了哪种现象发生。由于在膜中产生的应力具有速率依赖性，因此对于给定的系统，有两个临界膜张力值决定了这三种途径的边界。我们的发现为软粘性膜的弹道冲击响应提供了广泛的物理见解，并为使用微/纳米级弹道工具通过脂质膜进行药物输送提供了设计策略。
