Biology subjects

Geiger, B. J.

Publications and source records attributed to Geiger, B. J..

3 recordsLinked to original sources

bioRxiv2026

Insights into Spontaneous Curvature in Complex Membranes from Dual-Tether Pulling Experiments

Spontaneous curvature characterizes the propensity of a membrane to bend in a specific direction. It is therefore crucial in the multitude of cellular processes that involve membrane shape remodelling. Yet, experimentally quantifying the spontaneous curvature remains a significant challenge in complex biological membranes, as their heterogeneity causes ambiguities in spontaneous curvatures physical interpretation. Here, we introduce a general experiment-simulation framework to measure an effective spontaneous curvature using dual-direction tether pulling from cell-attached giant plasma membrane vesicles (GPMVs) and mesoscale simulations. For homogeneous membranes, the force difference between inward and outward pulls yields a tension-independent readout of spontaneous curvature. We show that this continuum observable can be generalized to the mean of the spontaneous curvature in a heterogeneous membrane, independent of the underlying microscopic spontaneous curvature distribution. Applied to HEK-derived GPMVs, a baseline negative spontaneous curvature of the plasma membrane is revealed. Sucrose treatment and extracellular addition of Annexin A5 systematically shift the effective spontaneous curvature, while mucin reporter overexpression does not measurably alter it under the conditions tested. We also measure the curvature imprint of individual fluorescently tagged proteins through a sorting index. Benchmarked with Annexin A5, our scheme recovers curvature imprints very similar to previous atomistic molecular dynamics simulations. Taken together this makes spontaneous curvature accessible as a directly measurable material property of native membranes and membrane-proteins, enabling quantitative studies of membrane remodelling across diverse cellular processes.

biophysics↗

bioRxiv2025

TS2CG as a membrane builder

Molecular dynamics (MD) simulations excel at capturing biological processes at the molecular scale but rely on a well-defined initial structure. As MD simulations now extend to whole-cell-level modeling, new tools are needed to efficiently build initial structures. Here, we introduce TS2CG version 2, designed to construct coarse-grained membrane structures with any desired shape and lateral organization. This version enables precise placement of lipids and proteins based on curvature preference, facilitating the creation of large, near-equilibrium membranes. Additional features include controlled pore generation and the placement of specific lipids at membrane edges for stabilization. Moreover, a Python interface allows users to extend functionality while maintaining the high performance of the C++ core. To demonstrate its capabilities, we showcase challenging simulations, including a Mobius strip membrane, a vesicle with lipid domain as continental plates (Martini globe), and entire mitochondrial membranes exhibiting lipid heterogeneity due to curvature, along with a comprehensive set of tutorials.

biophysics↗

bioRxiv2025

Complex mechanical response of stomatocyte morphology: Implications for the nuclear envelope.

Among the fascinating shapes that biomembranes exhibit are stomatocytes with multiple membrane necks, found for example in nuclear membranes and open autophagosomes. These morphologies, characterised by a high topological genus, can be visualised as spherical double membranes connected by neck-like structures. The necks are often occupied by specific biomolecular complexes, such as the nuclear pore complex, which divide the space into three distinct compartments. Understanding how the size of these necks responds to pressure gradients is fundamentally important for unravelling the influence of mechanical stimuli on traffic control through the necks, for example, in nuclear mechanosensing. In this work, we use computer simulations and theoretical analysis to investigate how neck size responds to variations in pressure or tension. Our findings reveal a two-phase behaviour: below a certain threshold, necks constrict as the pressure gradient increases, while above that threshold, they dilate. This response stems from the pure membranes mechanics and depends on the magnitude of the pressure gradient, the initial diameter of the neck and the membrane bending rigidity. We also provide a simple equation that links the threshold tension, the neck diameter and the bending rigidity, offering a useful tool to quickly assess different scenarios. Our results furthermore show that protein complexes in the neck partially counteract both constriction and dilation, stabilising neck size while preserving the same two-phase response to membrane tension. These findings uncover a promising, previously overlooked membrane property with implications for organelle shape and function, as well as for synthetic membrane design.

biophysics↗