Published November 5, 2021 | Version Published
Journal article Open

Modulating the pro-apoptotic activity of cytochrome c at a biomimetic electrified interface

Creators

  • 1. The Bernal Institute and Department of Chemical Sciences, School of Natural Sciences, University of Limerick (UL), Limerick V94 T9PX, Ireland
  • 2. The Bernal Institute and Department of Physics, School of Natural Sciences, University of Limerick (UL), Limerick V94 T9PX, Ireland
  • 3. Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, Université de Lorraine, CNRS, LCPME, F-54000 Nancy, France

Description

Programmed cell death via apoptosis is a natural defence against excessive cell division, crucial for foetal development to maintenance of homeostasis and elimination of precancerous and senescent cells. Here we demonstrate an electrified liquid bio-interface 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. Remarkably, we observe interfacial electron transfer between an organic electron donor decamethylferrocene and O2, electrocatalysed 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 bio-interface to identify drug molecules, such as bifonazole, that can potentially downregulate Cyt c and protect against uncontrolled neuronal cell death in neurodegenerative disorders.

Notes

D.T. thanks Science Foundation Ireland (SFI) for computing resources at the SFI/Higher Education Authority Irish Center for High-End Computing (ICHEC). A.G.-Q. acknowledges funding received from an Irish Research Council (IRC) Government of Ireland Postdoctoral Fellowship Award (Grant Number GOIPD/2018/252). G.H. and M.D. are grateful to the French Programme Investissement d'Avenir (PIA) "Lorraine Université d'Excellence" (Reference no. ANR-15-IDEX-04-LUE). M.D.S. and G.H. are grateful to the support of the IRC and Campus France for travel support between the French and Irish groups through their joint ULYSSES programme. DT thanks Science Foundation Ireland (SFI) for support (awards Grant Numbers 15/CDA/3491 and 12/RC/2275_P2).

Files

2021_Science_Advances_Manuscript_Open_Access.pdf

Files (37.7 MB)

Name Size Download all
md5:f319b0d4e2e013ef23cc21e38c09db3b
1.2 MB Preview Download
md5:cc5b3af8dceec6d664f69909d3adaafb
4.2 MB Preview Download
md5:5e2be4e87155a25f699ee19621ffe69c
14.2 MB Preview Download
md5:677a7d6292527f952792cd59939c5266
18.1 MB Preview Download

Additional details

Funding

Science Foundation Ireland
Designing Reactive Functionalised Soft Interfaces _ Self-healing soft materials for solar energy conversion, energy storage, and sustainable low cost hydrogen production 13/SIRG/2137
European Commission
SOFT-PHOTOCONVERSION – Solar Energy Conversion without Solid State Architectures: Pushing the Boundaries of Photoconversion Efficiencies at Self-healing Photosensitiser Functionalised Soft Interfaces 716792