Lea Rems (Author), Xinru Tang (Author), Fangwei Zhao (Author), Sergio Pérez-Conesa (Author), Ilaria Testa (Author), Lucie Delemotte (Author)

Abstract

The plasma membrane of a biological cell is a complex assembly of lipids and membrane proteins, which tightly regulate transmembrane transport. When a cell is exposed to strong electric field, the membrane integrity becomes transiently disrupted by formation of trans-membrane pores. This phenomenon termed electroporation is already utilized in many rapidly developing applications in medicine including gene therapy, cancer treatment, and treatment of cardiac arrhythmias. However, the molecular mechanisms of electroporation are not yet sufficiently well understood; in particular, it is unclear where exactly pores form in the complex organization of the plasma membrane. In this study, we combine coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis to identify how formation of pores depends on the local lipid organization. We show that pores do not form homogeneously across the membrane, but colocalize with domains that have specific features, the most important being high density of polyunsaturated lipids. We further show that knowing the lipid organization is sufficient to reliably predict poration sites with machine learning. Additionally, by analysing poration kinetics with Bayesian survival analysis we show that poration does not depend solely on local lipid arrangement, but also on membrane mechanical properties and the polarity of the electric field. Finally, we discuss how the combination of atomistic and coarse-grained molecular dynamics simulations, machine learning methods, and Bayesian survival analysis can guide the design of future experiments and help us to develop an accurate description of plasma membrane electroporation on the whole-cell level. Achieving this will allow us to shift the optimization of electroporation applications from blindtrial- and- error approaches to mechanistic-driven design.

Keywords

celična membrana;električno polje;pore;simulacije molekularne dinamike;strojno učenje;Bayesova analiza preživetja;plasma membrane;electric field;pores;molecular dynamics simulation;machine learning;Bayesian survival analysis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FE - Faculty of Electrical Engineering
UDC: 577
COBISS: 100814851 Link will open in a new window
ISSN: 2050-084X
Views: 8
Downloads: 3
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: celična membrana;električno polje;pore;simulacije molekularne dinamike;strojno učenje;Bayesova analiza preživetja;
Type (COBISS): Article
Pages: str. 1-26
Volume: ǂVol. ǂ11
Issue: e74773
Chronology: 2022
DOI: 10.7554/eLife.74773
ID: 21465744