Biology subjects

Liebl, K.

Publications and source records attributed to Liebl, K..

3 recordsLinked to original sources

bioRxiv2025

Membrane Remodeling by the Collective Action of Caveolin-1

Caveolin-1 proteins scaffold 50-100nm large invaginations in the plasma membrane to mediate critical cellular processes. As revealed recently by cryo-electron microscopy, several caveolin-1 protomers can fold into a disk-like structure that embeds in the cytoplasmic leaflet. This 8S complex represents a basal component to drive membrane curvature via higher-order interactions. The biophysical mechanisms behind the membrane remodeling, however, have remained elusive. To address this shortcoming, we have developed a new bottom-up coarse-grained model to overcome the substantial computational limitations for this large system. During simulations with the coarse-grained model, the complexes increasingly coordinate as partially mediated by attractive electrostatic interactions between scaffolding domains. The coordination of complexes strongly correlates with membrane protrusion, as approaching complexes amplify localized stress in the exoplasmic leaflet. Thus, proximity of two CAV1-8S complexes induces dynamic curvature generation that can facilitate access for signaling partners. This mechanism is further explored in clusters of multiple CAV1-8S complexes that form large-scale membrane invaginations.

biophysics↗

bioRxiv2025

Deciphering DNA's sequence-dependent structure and deformability with normalizing flows

The sequence-dependent structure and deformability of double-stranded DNA plays a key role in many cellular processes. Accurate description thereof has thus been a long-standing problem. Previous approaches to this problem assume a specific functional form for the elastic energy in terms of internal coordinates of the DNA double-helix. The conformational flexibility of DNA, however, is strongly impacted by several stereo-chemical effects that complicate the formulation of an accurate functional form. In this work, I propose an entirely new, AI-based method to decipher the sequence-dependent structure and deformability of double-stranded DNA. This method employs normalizing flows that capture multimodal and correlation effects between internal coordinates of the DNA double helix excellently, and hence allows one to accurately quantify deformation energies for any double-stranded DNA structure and sequence. Thus, it offers a wide range of future applications, and speaks in favor of AI-based elasticity-descriptions also for other molecules.

biophysics↗

bioRxiv2024

Lipid Organization by the Caveolin-1 Complex

Caveolins are lipid-binding proteins that can organize membrane remodeling and oligomerize into the 8S-complex. The CAV1 8S-complex comprises a disk-like structure, about 15nm in diameter, with a central beta barrel. Further oligomerization of 8S-complexes remodels the membrane into caveolae vessels, with a dependence on cholesterol concentration. However, the molecular mechanisms behind membrane remodeling and cholesterol filtering are still not understood. Performing atomistic Molecular Dynamics simulations in combination with advanced sampling techniques, we describe how the CAV1-8S complex bends the membrane and accumulates cholesterol. Here, our simulations show an enhancing effect by the palmitoylations of CAV1, and we predict that the CAV1-8S complex can extract cholesterol molecules from the lipid bilayer and accommodate them in its beta barrel. Through backmapping to the all-atom level we also conclude that the Martini v2 coarse-grained forcefield overestimates membrane bending, as the atomistic simulations exhibit only very localized bending.

biophysics↗