Richards Ceri J, Ahmadi Majid, Stuart Marc C A, Kooi Bart J, Åberg Christoffer, Roos Wouter H
Molecular Biophysics, Zernike Institute for Advanced Materials, Rijksuniversiteit Groningen, 9747 AG Groningen, Netherlands.
Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, Rijksuniversiteit Groningen, 9713 AV Groningen, Netherlands.
Nanoscale. 2022 Dec 22;15(1):248-258. doi: 10.1039/d2nr05296b.
The current lack of insight into nanoparticle-cell membrane interactions hampers smart design strategies and thereby the development of effective nanodrugs. Quantitative and methodical approaches utilizing cell membrane models offer an opportunity to unravel particle-membrane interactions in a detailed manner under well controlled conditions. Here we use total internal reflection microscopy for real-time studies of the non-specific interactions between nanoparticles and a model cell membrane at 50 ms temporal resolution over a time course of several minutes. Maintaining a simple lipid bilayer system across conditions, adsorption and desorption were quantified as a function of biomolecular corona, particle size and fluid flow. The presence of a biomolecular corona reduced both the particle adsorption rate onto the membrane and the duration of adhesion, compared to pristine particle conditions. Particle size, on the other hand, was only observed to affect the adsorption rate. The introduction of flow reduced the number of adsorption events, but increased the residence time. Lastly, altering the composition of the membrane itself resulted in a decreased number of adsorption events onto negatively charged bilayers compared to neutral bilayers. Overall, a model membrane system offers a facile platform for real-time imaging of individual adsorption-desorption processes, revealing complex adsorption kinetics, governed by particle surface energy, size dependent interaction forces, flow and membrane composition.
目前对纳米颗粒与细胞膜相互作用的认识不足,阻碍了智能设计策略的发展,进而影响了有效纳米药物的开发。利用细胞膜模型的定量和系统方法提供了一个机会,能够在良好控制的条件下详细揭示颗粒与膜之间的相互作用。在这里,我们使用全内反射显微镜,以50毫秒的时间分辨率,在几分钟的时间过程中实时研究纳米颗粒与模型细胞膜之间的非特异性相互作用。在各种条件下保持一个简单的脂质双层系统,吸附和解吸被量化为生物分子冠、颗粒大小和流体流动的函数。与原始颗粒条件相比,生物分子冠的存在降低了颗粒在膜上的吸附速率和粘附持续时间。另一方面,仅观察到颗粒大小会影响吸附速率。流动的引入减少了吸附事件的数量,但增加了停留时间。最后,与中性双层相比,改变膜本身的组成导致在带负电荷的双层上的吸附事件数量减少。总体而言,模型膜系统为单个吸附 - 解吸过程的实时成像提供了一个便捷的平台,揭示了由颗粒表面能、尺寸依赖性相互作用力、流动和膜组成所控制的复杂吸附动力学。