Gamero-Quijano Alonso, Bhattacharya Shayon, Cazade Pierre-André, Molina-Osorio Andrés F, Beecher Cillian, Djeghader Ahmed, Soulimane Tewfik, Dossot Manuel, Thompson Damien, Herzog Grégoire, Scanlon Micheál D
The Bernal Institute, University of Limerick (UL), Limerick V94 T9PX, Ireland.
Department of Chemical Sciences, School of Natural Sciences, University of Limerick (UL), Limerick V94 T9PX, Ireland.
Sci Adv. 2021 Nov 5;7(45):eabg4119. doi: 10.1126/sciadv.abg4119.
Programmed cell death via apoptosis is a natural defence against excessive cell division, crucial for fetal development to maintenance of homeostasis and elimination of precancerous and senescent cells. Here, we demonstrate an electrified liquid biointerface that replicates the molecular machinery of the inner mitochondrial membrane at the onset of apoptosis. By mimicking in vivo cytochrome c (Cyt c) interactions with cell membranes, our platform allows us to modulate the conformational plasticity of the protein by simply varying the electrochemical environment at an aqueous-organic interface. We observe interfacial electron transfer between an organic electron donor decamethylferrocene and O, electrocatalyzed by Cyt c. This interfacial reaction requires partial Cyt c unfolding, mimicking Cyt c in vivo peroxidase activity. As proof of concept, we use our electrified liquid biointerface to identify drug molecules, such as bifonazole, that can potentially down-regulate Cyt c and protect against uncontrolled neuronal cell death in neurodegenerative disorders.
通过凋亡进行的程序性细胞死亡是对抗细胞过度分裂的一种自然防御机制，对于胎儿发育、维持体内平衡以及消除癌前细胞和衰老细胞至关重要。在此，我们展示了一种带电液体生物界面，它在凋亡开始时复制线粒体内膜的分子机制。通过模拟体内细胞色素c（Cyt c）与细胞膜的相互作用，我们的平台使我们能够通过简单改变水 - 有机界面的电化学环境来调节蛋白质的构象可塑性。我们观察到有机电子供体十甲基二茂铁与O之间的界面电子转移，这是由Cyt c电催化的。这种界面反应需要Cyt c部分展开，模拟了Cyt c在体内的过氧化物酶活性。作为概念验证，我们使用我们的带电液体生物界面来鉴定药物分子，如联苯苄唑，其可能下调Cyt c并预防神经退行性疾病中不受控制的神经元细胞死亡。
