Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
ACS Nano. 2013 Dec 23;7(12):10960-70. doi: 10.1021/nn404481f. Epub 2013 Nov 20.
Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The protein corona can significantly influence particle-cell interactions, including internalization and pathway activation. In this work, we demonstrate the differential roles of a given protein corona formed in cell culture media in particle uptake by monocytes and macrophages. By exposing disulfide-stabilized poly(methacrylic acid) nanoporous polymer particles (PMASH NPPs) to complete cell growth media containing 10% fetal bovine serum, a protein corona, with the most abundant component being bovine serum albumin, was characterized. Upon adsorption onto the PMASH NPPs, native bovine serum albumin (BSA) was found to undergo conformational changes. The denatured BSA led to a significant decrease in internalization efficiency in human monocytic cells, THP-1, compared with the bare particles, due to reduced cell membrane adhesion. In contrast, the unfolded BSA on the NPPs triggered class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like cells (dTHP-1) without a significant impact on the overall internalization efficiency. Taken together, this work demonstrates the disparate effects of a given protein corona on particle-cell interactions, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities.
许多生物分子，主要是蛋白质，会吸附在聚合物颗粒上，在生物环境中形成动态的蛋白质冠。蛋白质冠可以显著影响颗粒与细胞的相互作用，包括内化和途径激活。在这项工作中，我们证明了在细胞培养介质中形成的给定蛋白质冠在单核细胞和巨噬细胞摄取颗粒中的差异作用。通过将二硫键稳定的聚（甲基丙烯酸）纳米多孔聚合物颗粒（PMASH NPPs）暴露于含有 10%胎牛血清的完整细胞生长培养基中，对含有最丰富成分牛血清白蛋白（BSA）的蛋白质冠进行了表征。在吸附到 PMASH NPPs 上后，发现天然 BSA 发生了构象变化。与裸颗粒相比，变性的 BSA 导致人单核细胞（THP-1）的内化效率显著降低，这是由于细胞膜粘附减少所致。相比之下，NPPs 上的展开 BSA 在分化的巨噬细胞样细胞（dTHP-1）中触发了 A 类清道夫受体介导的吞噬作用，而对整体内化效率没有显著影响。综上所述，这项工作证明了给定蛋白质冠对颗粒与细胞相互作用的不同影响，突出了蛋白质冠构象与相关生物学特性之间的相关性，这对于生物功能至关重要。
