Adsorption and Unfolding of a Single Protein Triggers Nanoparticle Aggregation

The response of living systems to
nanoparticles is thought to depend
on the protein corona, which forms shortly after exposure to physiological
fluids and which is linked to a wide array of pathophysiologies. A
mechanistic understanding of the dynamic interaction between proteins
and nanoparticles and thus the biological fate of nanoparticles and
associated proteins is, however, often missing mainly due to the inadequacies
in current ensemble experimental approaches. Through the application
of a variety of single molecule and single particle spectroscopic
techniques in combination with ensemble level characterization tools,
we identified different interaction pathways between gold nanorods
and bovine serum albumin depending on the protein concentration. Overall,
we found that local changes in protein concentration influence everything
from cancer cell uptake to nanoparticle stability and even protein
secondary structure. We envision that our findings and methods will
lead to strategies to control the associated pathophysiology of nanoparticle
exposure in vivo.

人们普遍认为，生命系统对纳米颗粒的响应取决于蛋白冠（protein corona）：该结构会在纳米颗粒暴露于生理流体后短时间内形成，并与多种病理生理状态密切相关。然而，目前人们往往缺乏对蛋白质与纳米颗粒之间动态相互作用的机制性认知，也难以阐明纳米颗粒及其结合蛋白的生物学归趋，这一局限主要源于当前整体实验方法存在诸多不足。本研究通过将多种单分子（single molecule）、单粒子（single particle）光谱技术与整体水平表征工具相结合，发现金纳米棒（gold nanorods）与牛血清白蛋白（bovine serum albumin）之间的相互作用路径会随蛋白质浓度的变化而有所差异。总体而言，本研究发现蛋白质浓度的局部变化会影响多个层面的过程——从癌细胞摄取、纳米颗粒稳定性，乃至蛋白质二级结构均受其调控。我们预计，本研究的发现与方法将助力开发出调控体内（in vivo）纳米颗粒暴露相关病理生理状态的策略。