College 8 Seminar | Neutrons for Health: Lipid Asymmetry, Fluctuations, and Protein Interactions in Biological Membranes

Biological membranes are complex systems whose function is critically governed by lipid asymmetry, thermal fluctuations, and protein interactions. In this talk, I present an integrated experimental–theoretical approach to investigate membrane structure and dynamics using neutron and X-ray scattering techniques.

In the first part, I show how structure and dynamics of myelin-mimetic membranes can be studied using neutron scattering methods [1, 2]. Selective deuteration of lipid components enables leaflet-specific contrast, revealing that the interaction with the Myelin Basic Protein (MBP) is strongly modulated by membrane asymmetry. Physiological membrane asymmetry promotes stable, surface-bound MBP configurations, whereas diseased or symmetrized membranes exhibit weakened binding and altered protein insertion. Temperature-dependent measurements further demonstrate that lipid asymmetry in myelin-mimetic membranes is thermally unstable in the absence of biological regulatory mechanisms.

In the second part, I will introduce a Gaussian model of fluctuating membranes that provides a unified framework for the joint analysis of elastic (SANS/SAXS) and inelastic (NSE) scattering data [3, 4]. The model consistently captures bending and thickness fluctuations across multiple membrane sublayers, enabling a direct coupling between membrane structure and dynamics. Applications to biologically derived neuronal membranes demonstrate that structural and dynamic parameters can be robustly determined within a single model [3]. Finally, I will present how this framework can be extended to membranes with protein inclusions. The extension describes transmembrane and peripheral proteins with low-resolution embedded within the membrane. This mathematical approach allows protein–membrane correlations to be treated consistently in both elastic and inelastic scattering experiments. The model has been applied to the study of protein-rich red blood cell membranes [4].

1. Krugmann et al. Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis. Sci Rep (2020) 10, 16691

2. Pusterla et al. Myelin Basic Protein Binding Is Modulated by Leaflet Asymmetry and Lipid Composition, in review; preprint: doi.org/10.64898/2025.12.19.695364

3. Gommes et al. Gaussian model of fluctuating membrane and its scattering properties. Phys. Rev. E (2024) 110, 034608

4. Gommes et al. Model for small-angle scattering analysis of membranes with protein-like inclusions. J. Appl. Cryst. (2025). 58, 1571-1581