Fighting disease with digital simulations

What is a lipid membrane?

Lipid membranes are ubiquitous structures in the cells of all unicellular and multicellular organisms. Take, for example, the cell wall, also known as the plasma membrane, whose function is to separate the inside of the cell from the outside: in a way, it’s the cell’s armor. It’s made up of a vast diversity of fatty acids (lipids), which give it very special properties. If we consider the enormous variety of lipid species available, we can begin to grasp the enormous complexity of this system.

It had already been observed that changes in the composition of lipid membranes can be indicative of the presence of certain diseases, such as cancer, type 2 diabetes, Alzheimer’s and Parkinson’s diseases. Knowing the composition of lipid membranes in diseased cells, and comparing it with that of a healthy cell, would undoubtedly lead to new ways of diagnosing these diseases. However, experimental studies of cell membrane organization remain technically difficult. Fortunately, computer simulations can help fill in the missing information. Thus, molecular modeling is proving to be a crucial tool for studying the morphology of complex systems and providing real-time three-dimensional images of these systems with atomistic resolution.

LUMI, a European supercomputer

The LUMI (Large Unified Modern Infrastructure) supercomputer is one of the components of the European Joint Undertaking for High-Performance Computing (HPC), known as EuroHPC JU. The latter coordinates the pooling of European resources to develop high-end supercomputers for large-scale data processing and complex calculations. More specifically, LUMI is the fastest supercomputer in Europe and the^5th fastest worldwide. Located in Finland, it is managed by the LUMI consortium, of which Belgium is a member, alongside Finland, the Czech Republic, Denmark, Estonia, Iceland, Norway, Poland, Sweden and Switzerland.

This consortium provides a high-quality, cost-effective and environmentally sustainable HPC ecosystem (a power supply based on the use of hydroelectricity, while the surplus is used to heat the nearby town). At the heart of the consortium’s expertise lies a strong tradition of collaboration in HPC training and education, user support and data management services.

The Namur research team used LUMI’s supercomputing power to push back the limits of our current knowledge. They were able to study in detail the evolution of a realistic plasma membrane with a composition similar to that of a healthy cell. Including no fewer than 42 different lipid types covering a wide variety of lipids, and cholesterol molecules, for a total of over 3 million atoms, this work represents a truly computational feat. More specifically, they investigated the influence of lipid composition on the non-linear optical (NLO) response of probe molecules, chromophores, inserted into membranes of increasing complexity. Non-linear optics is a highly sensitive analysis technique, and the aim of this study was to verify that the environment of the chromophores, and therefore the composition of the membrane, induced sufficiently significant changes in this ONL response to be detected.

To achieve this, numerical simulations were used. They combine molecular dynamics (to know the temporal evolution of the system) and quantum chemistry calculations (to predict the ONL response). Then, by combining the results obtained with machine learning tools, it was possible to highlight the factors influencing the ONL response in this complex environment, paving the way for the study of other cell membranes, this time typical of diseased cells.

Image caption: Simulation ofan ideal plasma membrane including no less than 42 different lipid types and covering a wide variety of lipids (phosphatidic acid [PA], phosphatitylcholine [PC], phosphatitylethanolamine [PE], phosphatitylinositol [PI], phosphatitylserine [PS], sphingomyelin [SM], and diaglycerol [DAG]), cholesterol molecules [CHL], as well as probe molecules [di-8-ANEPPS] with a non-linear optical response [ONL], for a total of over 3 million atoms.atoms.

Overall, this work represents a first step towards understanding the cooperation, synergy and interactions that occur in lipid membranes, and opens up new avenues for drug design in the field of membrane lipid therapy.

Journal of Chemical Information and Modeling: "Multimillion Atom Simulations of Di-8-ANEPPS Chromophores Embedded in a Model Plasma Membrane: Toward the Investigation of Realistic Dyed Cell Membranes"

• 1992 : Docteur en Sciences (UNamur)
• 1994 : Prix IBM Belgium
• 2001 : Agrégé de l’Enseignement Supérieur (UNamur)
• 2012-2015 : Francqui Research Professor
• 2010-2016: President of the Consortium des Équipements de Calcul Intensif (CÉCI
)
• 2020: Chemistry Europe Fellow
• Director of Chimie Nouvelle magazine


Member of the High Performance Computing (HPC) Multiscale Modelling cluster at the Namur Institute of Structured Matter (NISM)

The 50th anniversary of the first graduating class of the UNamur Chemistry Department will be celebrated on Saturday, April 20, 2024 at UNamur, in the afternoon and evening. More info...

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