Sanchez-Guzman Daniel, Giraudon-Colas Gaël, Marichal Laurent, Boulard Yves, Wien Frank, Degrouard Jéril, Baeza-Squiban Armelle, Pin Serge, Renault Jean Philippe, Devineau Stéphanie
Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France.
Université Paris-Saclay, CEA, CNRS, NIMBE, Gif-sur-Yvette 91190, France.
ACS Nano. 2020 Jul 28;14(7):9073-9088. doi: 10.1021/acsnano.0c04165. Epub 2020 Jul 7.
Few experimental techniques allow the analysis of the protein corona . As a result, little is known on the effects of nanoparticles on weakly bound proteins that form the soft corona. Despite its biological importance, our understanding of the molecular bases driving its formation is limited. Here, we show that hemoglobin can form either a hard or a soft corona on silica nanoparticles depending on the pH conditions. Using cryoTEM and synchrotron-radiation circular dichroism, we show that nanoparticles alter the structure and the stability of weakly bound proteins . Molecular dynamics simulation identified the structural elements driving protein-nanoparticle interaction. Based on thermodynamic analysis, we show that nanoparticles stabilize partially unfolded protein conformations by enthalpy-driven molecular interactions. We suggest that nanoparticles alter weakly bound proteins by shifting the equilibrium toward the unfolded states at physiological temperature. We show that the classical approach based on nanoparticle separation from the biological medium fails to detect destabilization of weakly bound proteins, and therefore cannot be used to fully predict the biological effects of nanomaterials .
很少有实验技术能够分析蛋白质冠层。因此，对于纳米颗粒对形成软冠层的弱结合蛋白的影响知之甚少。尽管其具有生物学重要性，但我们对驱动其形成的分子基础的理解仍然有限。在这里，我们表明血红蛋白在二氧化硅纳米颗粒上可根据pH条件形成硬冠层或软冠层。使用低温透射电子显微镜和同步辐射圆二色性，我们表明纳米颗粒会改变弱结合蛋白的结构和稳定性。分子动力学模拟确定了驱动蛋白质-纳米颗粒相互作用的结构元件。基于热力学分析，我们表明纳米颗粒通过焓驱动的分子相互作用稳定部分未折叠的蛋白质构象。我们认为，纳米颗粒通过在生理温度下将平衡向未折叠状态移动来改变弱结合蛋白。我们表明，基于从生物介质中分离纳米颗粒的经典方法无法检测到弱结合蛋白的去稳定化，因此不能用于全面预测纳米材料的生物学效应。
