Biology subjects

Heuvingh, J.

Publications and source records attributed to Heuvingh, J..

5 recordsLinked to original sources

bioRxiv2026

Softer when Thicker: a Conserved Scaling Law Governs Actin Cortex Mechanics

Scaling laws are powerful tools in material science to relate geometric and mechanical properties of materials. The actin cortex, a dynamic network beneath the plasma membrane, is essential for cellular morphogenesis, force generation, and tissue organization. Despite its critical role, the mechanical properties of the cortex itself remain poorly understood. Using the magnetic pincher, a new technique we recently developed, we directly measure the thickness (h) and elastic modulus (E) of the actin cortex in live cells, uncovering a universal scaling (E ~ h-2) across multiple cell types. Drawing an analogy to cellular solids, common in nature and material science, we identified an origin for this scaling: the volume fraction of actin filaments varies concomitantly with the cortex thickness, due to a conservation of filamentous actin quantity. Thus thinner cortices exhibit higher actin density and stiffness, while thicker cortices are sparser and softer. The relationship holds under diverse perturbations targeting myosin contractility, actin nucleation, and turnover, but is lost upon actin disassembly, highlighting its dependence on the intact actin network. Our results establish that cells, across cell types, function within a rather limited range of quantity of cortical actin filaments and primarily modulate cortex thickness to tune mechanical properties, with profound implications for cell shape regulation, tissue mechanics, and the interpretation of indentation-based mechanical measurements.

biophysics↗

bioRxiv2025

Asymmetric phosphoinositide lipid bilayers generated by spontaneous lipid insertion

Phosphatidylinositol phosphate (PIP) lipids, enriched on the cytoplasmic leaflet of the plasma membrane, are key regulators of diverse cellular processes, often through interactions with partner proteins that regulate actin assembly. Supported lipid bilayers (SLBs) provide a powerful model system to study the interactions of PIP lipids with their partner proteins. However, despite advances in SLB preparation methods, it remains a challenge to robustly obtain fluid SLBs in which PIP lipids are both mobile and asymmetrically distributed. In this study, we report a simple and robust method to generate asymmetric SLBs containing tunable amounts of PI(4,5)P2. By dissolving PI(4,5)P2 below its critical micelle concentration (CMC), we enable its spontaneous insertion into the upper leaflet of SLBs exposed to bulk solution. The mobility of PI(4,5)P2 is confirmed using fluorescence recovery after photobleaching (FRAP). Furthermore, we demonstrate that PI(4,5)P2 incorporated using this method retains its functionality, recruiting binding partners, actin-membrane linker ezrin, and myosin 1 motors capable of sliding actin filaments on the SLBs. Our method offers a straightforward strategy to generate asymmetric PI(4,5)P2-containing SLBs and is applicable to other lipid species with high CMC values.

biophysics↗

bioRxiv2023

The membrane-actin linkers ezrin, radixin, and moesin are dispensable for macrophage migration and cortex mechanics.

The cellular actin cortex provides crucial mechanical support and plays critical roles in numerous functions, including cell division and migration. The proteins of the ERM family, ezrin, radixin, and moesin, are central to these processes by linking the plasma membrane to the actin cytoskeleton. To investigate the individual contributions of these three proteins to leukocyte migration, we generated single and triple ERM knock-out macrophages. Surprisingly, we found that even in the absence of ERMs, macrophages can still form the different actin structures promoting cell migration, such as filopodia, lamellipodia, podosomes, and ruffles. Furthermore we discovered that, unlike every other cell type previously investigated, the single or triple knock-out of ERMs does not affect macrophage migration in a large diversity of contexts. Finally, we demonstrated that the loss of ERMs in macrophages does not affect the mechanics of their actin cortex. These findings challenge the notion that ERMs are universally essential for cortex mechanics and cell migration and support the notion that the macrophage cortex may have diverged from that of other cells to allow for their adaptive cortical plasticity.

cell biology↗

bioRxiv2023

The distance between the plasma membrane and the actomyosin cortex acts as a nanogate to control cell surface mechanics

Animal cell shape changes are controlled by the actomyosin cortex, a peripheral actin network tethered to the plasma membrane by membrane-to-cortex attachment (MCA) proteins. Previous studies have focused on how myosin motors or actin turnover can generate the local deformations required for morphogenesis. However, how the cell controls local actin nucleation remains poorly understood. By combining molecular engineering with biophysical approaches and in situ characterization of cortical actin network architecture, we show that membrane-to-cortex tethering determines the distance between the plasma membrane and the actomyosin cortex at the nanoscale of single actin nucleators. In turn, the size of this gap dictates actin filament production and the mechanical properties of the cell surface. Specifically, it tunes formin activity, controlling actin bundling and cortical tension. Our study defines the membrane-to-cortex distance as a nanogate that cells can open or close by MCA proteins to control the activity of key molecules at the cell surface.

biophysics↗

bioRxiv2020

Pinching the cortex of live cells reveals thickness instabilities caused by Myosin II motors

The cell cortex is a contractile actin meshwork, which determines cell shape and is essential for cell mechanics, migration and division. Because the cortical thickness is below optical resolution, it has been generally considered as a thin uniform two-dimensional layer. Using two mutually attracted magnetic beads, one inside the cell and the other in the extracellular medium, we pinch the cortex of dendritic cells and provide an accurate and time resolved measure of its thickness. Our observations draw a new picture of the cell cortex as a highly dynamic layer, harboring large fluctuations in its third dimension due to actomyosin contractility. We propose that the cortex dynamics might be responsible for the fast shape changing capacity of highly contractile cells that use amoeboid-like migration.

biophysics↗