Mitja Drab

This study theoretically investigates how anisotropic curved membrane components (CMCs) control vesicle morphology through curvature sensing, nematic alignment, topological defects and volume constraints.

This study theoretically investigates how anisotropic curved membrane components (CMCs) control vesicle morphology through curvature sensing, nematic alignment, topological defects, and volume constraints. By comparing arc-shaped and saddle-shaped CMCs, we identify a rich spectrum of steady-state phases. For fully CMC-covered vesicles, arc-shaped components drive a pearling-to-cylinder transition as nematic interactions strengthen, while on partially CMC-covered vesicles, the saddle-shaped CMCs stabilize necks between the convex regions of bare membrane. We map the steady-state shapes of vesicles partially covered by arc-like and saddle-shaped CMCs, exposing how different vesicle shapes depend on the interplay between nematic interactions and volume constraints, revealing several novel phases. By investigating the in-plane nematic field, we find that topological defects consistently localize to high-curvature regions, revealing how intrinsic and deviatoric curvature effects cooperate in membrane remodeling. These findings establish a unified framework for understanding how proteins and lipid domains with anisotropic intrinsic curvature shape cellular structures -- from organelle morphogenesis to global cell shape.

Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

Cell mechanics is a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material, but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

In this study, we implement the deviatoric curvature model to examine dynamically triangulated surfaces with anisotropic membrane inclusions. The Monte-Carlo numerical scheme is devised to not only minimize the total bending energy of the membrane but also the in-plane nematic order of the inclusions by considering the mismatch between the curvature of the membrane and the intrinsic curvature of the inclusion. Neighboring inclusions can either attract with nearest-neighbor interaction or with a nematic interaction derived from liquid crystal theory. Orientational order determines whether vesicles fully covered with inclusions result in bulbs connected by necks or long tubes. Remarkably, when inclusions on vesicles with no vacancies interact non-nematically, a spontaneous local order can lead to a bulb transition which may have implications in cell or organelle division. Furthermore we find that average nematic order is inversely proportional to the number of thin necks formed in the vesicles. Our method shows good convergence and is suitable for further upgrades, for example to vesicles constrained by volume.

Biological membranes are renowned for their intricate complexity, with the formation of membrane domains being pivotal to the successful execution of numerous cellular processes. However, due to their nanoscale characteristics, these domains are often understudied, as the experimental techniques required for quantitative investigation present significant challenges. In this study we employ spot-variation z-scan fluorescence correlation spectroscopy (svzFCS) tailored for artificial lipid vesicles of varying composition and combine this approach with high-resolution imaging. This method has been harnessed to examine the lipid-segregation behavior of distinct types of ceramide-1-phosphate (C1P), a crucial class of signaling molecules, within these membranes. Moreover, we provide a quantitative portrayal of the lipid membranes studied and the domains induced by C1P at both nano and microscales. Given the lack of definitive conclusions from the experimental data obtained, it was supplemented with comprehensive in silico studies—including the analysis of diffusion coefficient via molecular dynamics and domain populations via Monte Carlo simulations. This approach enhanced our insight into the dynamic behavior of these molecules within model lipid membranes, confirming that nano- and microdomains can co-exist in lipid vesicles.