Sloan-Dennison Sian, Schultz Zachary D
Department of Chemistry and Biochemistry , The Ohio State University , Columbus , OH 43210 , USA . Email:
Chem Sci. 2018 Dec 4;10(6):1807-1815. doi: 10.1039/c8sc05035j. eCollection 2019 Feb 14.
Protein-ligand recognition is a key activity where chemical signals are communicated to cells to activate various biochemical pathways, which are important for understanding membrane signaling and drug interactions. Gold nanostars are highly attractive for biological applications due to their readily modified surface chemistry, facile synthesis and optical properties. The increase in electromagnetic field at their branches increases the surface enhanced Raman scattering (SERS) making them ideal candidates as label free probes that can be used to detect a variety of cellular activities. However, the use of particles is complicated by the adsorption of proteins, which forms the protein corona. In this paper we demonstrate gold nanostars as label free probes to study the interaction between αβ integrin and RGD. Nanostars functionalized with cyclic-RDGFC reduced the formation of the protein corona, due to its zwitterionic nature, indicating a small peptide approach to minimizing protein absorption. Additionally, the functionalized nanostars evince a SERS response from their interaction with αβ integrin representative of the amino acids present at the binding site which is also retained in a complex biological matrix. The nanostars were used to selectively detect αβ integrin on the membrane of human metastatic colon cancer cells. By exploiting the intense SERS and tunable plasmon resonance properties of gold nanostars functionalized with cyclic RGDFC, we have demonstrated a label free approach to investigate the chemical interactions associated with protein-ligand binding from both purified proteins and membrane bound receptors in cells.
蛋白质 - 配体识别是一项关键活动,其中化学信号传递给细胞以激活各种生化途径,这对于理解膜信号传导和药物相互作用很重要。金纳米星因其易于修饰的表面化学、简便的合成方法和光学性质,在生物应用中极具吸引力。其分支处电磁场的增强增加了表面增强拉曼散射(SERS),使其成为可用于检测各种细胞活动的无标记探针的理想候选者。然而,蛋白质的吸附使颗粒的使用变得复杂,蛋白质吸附会形成蛋白质冠层。在本文中,我们展示了金纳米星作为无标记探针来研究αβ整合素与RGD之间的相互作用。用环 - RDGFC功能化的纳米星由于其两性离子性质减少了蛋白质冠层的形成,这表明一种通过小肽方法来最小化蛋白质吸附。此外,功能化的纳米星在与αβ整合素相互作用时表现出SERS响应,这代表了结合位点处存在的氨基酸,并且在复杂的生物基质中也能保留这种响应。这些纳米星被用于选择性检测人转移性结肠癌细胞膜上的αβ整合素。通过利用用环RGDFC功能化的金纳米星的强烈SERS和可调谐等离子体共振特性,我们展示了一种无标记方法,用于研究从纯化蛋白质和细胞中膜结合受体的蛋白质 - 配体结合相关的化学相互作用。