Thèse

Jeudi 16 Octobre 2025 à 15h00.

Electrostatics of charged lipid membranes: mesoscopic and molecular modelling

Ludovic GARDRE

Salle des thèses INL - Bâtiment Joliot Curie

Invité(e) par
Claire LOISON et Laurent JOLY

présentera en 2 heures :

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Directeur de thèse / thesis director :
Claire LOISON et Laurent JOLY

Membres du jury / jury members :
Hélène Berthoumieux
Laurent JOLY
Damien LAAGE
Claire LOISON
Jean-Paul RIEU
Alexander SCHLAICH

Résumé / Abstract :
This thesis is part of the "Banana Slip" project funded by the French National Research Agency, which aims to deepen our understanding of the role of lipid membranes in joint lubrication.
Because they are amphiphilic, lipids self-assemble in water to form, among other structures, lipid bilayers which are key components of cell membranes. Their presence in joints dramatically lowers the coefficient of friction, yet the molecular-scale mechanisms behind this lubrication are not fully elucidated. Notably, the composition of synovial fluid differs between osteoarthritis patients and healthy individuals. Tribological studies have shown that changing either the nature or even simply the proportion of the various lipids in synovial fluid can raise the friction coefficient.
A structural distinction exists between zwitterionic (electrically neutral) membranes and those composed of charged lipids. Paradoxically, the equilibrium distance between charged membranes can be smaller than between zwitterionic ones, despite the expected electrostatic repulsion. When lipids are charged, ions in the water confined between bilayers neutralize the membrane charge. In the presence of di- or trivalent ions, strong-coupling theory explains an attraction driven by their correlations. Yet our collaborators observed a similar attraction with monovalent ions. To account for this, the working hypothesis is a pronounced drop in the dielectric permittivity of the water confined between the bilayers. This property is difficult to probe experimentally at the nanoscale, and existing theoretical models for estimating its profile are limited either by system anisotropy or by the presence of free charges.
These observations motivated our research. We propose a model that yields an effective dielectric permittivity profile in systems containing free charges. We begin with zwitterionic membranes, where an approach based on the fluctuation-dissipation theorem allows us to determine the tangential and normal components of the dielectric permittivity profile. Because that approach is incompatible with free charges, we next develop a modified Poisson-Boltzmann model that incorporates spatially varying dielectric permittivity. In this model, the ion free-charge density is described analytically by a Boltzmann distribution augmented with a solvation energy term. For these charged systems, we assume that the dielectric permittivity does not differ fundamentally from that observed in zwitterionic systems. We therefore represent it with a functional form inspired by the uncharged case.
We then apply this modified Poisson-Boltzmann model to obtain dielectric permittivity profiles across a wide range of membrane hydration states and temperatures, before discussing the resulting values and the model’s limitations.
Finally, we refine our simulation models to more closely match experimental systems. These new simulations first provide data for an experimental study, enabling, among other things, the determination of certain parameters in the model used for the analysis. We then construct membranes made of mixed zwitterionic and charged lipids. In these systems, we again apply the modified Poisson-Boltzmann model to study how surface charge influences dielectric permittivity. Lastly, we present a protocol for simulating supported lipid bilayers.''