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BP: Fachverband Biologische Physik
BP 4: Computational Biophysics II
BP 4.1: Hauptvortrag
Montag, 9. März 2026, 15:00–15:30, BAR/SCHÖ
The Multi-faceted Role of Cholesterol in Cellular Membranes and Lipid Nanoparticles — •Rainer Böckmann — Computational Biology - Theoretical & Computational Membrane Biophysics, Friedrich-Alexander-Universität Erlangen-Nürnberg
Cellular membranes serve as dynamic interfaces regulating numerous biological processes, with cholesterol playing a central role in shaping their structure, dynamics, and function. Likewise, cholesterol is crucial for stabilizing lipid nanoparticles (LNPs) in pharmaceutical applications and for enhancing their therapeutic efficacy. Here, we elucidate the multifaceted functions of cholesterol in both biological membranes and LNPs using atomistic molecular dynamics simulations, including constant-pH approaches.
Our findings challenge conventional views of membrane organization by revealing that thermal membrane bending and local cholesterol distribution can collaborate to soften membranes [1], even though cholesterol is widely associated with membrane thickening and reduced permeability. Turning to lipid nanoparticles, we demonstrate that cholesterol is significantly enriched in the LNP shell [2], resulting in shifts of the pKa of aminolipids by 2-4 units, contingent on the specific lipid composition [3]. This insight underscores the importance of cholesterol-lipid interactions in modulating the physicochemical properties of LNPs, with direct implications for the design and optimization of cholesterol-containing nanocarriers in drug delivery. [1] Pöhnl et al. Nat.Commun. 14, 8038 (2023) [2] Trollmann, Böckmann. Biophys.J. 121, 3927 (2022) [3] Trollmann, Böckmann. Small (2026)
Keywords: cholesterol; lipid nanoparticle; constant-pH molecular dynamics simulation; diffusional softening