Avinoam Lab

Membrane Remodeling & Muscle Biology

Research

Welcome to the Membrane Remodeling Lab! We are a dedicated team of scientists, fascinated by the dynamic world of biological membranes.

Dynamic membrane remodeling defines and connects all cellular life. Biological membranes shape cells and their internal compartments, while controlling the movement of materials and information within and between cells. Because membranes are fundamental to cellular organization, understanding how they are remodeled is central to understanding biology.

Membrane remodeling drives core cellular processes such as endocytosis, exocytosis, organelle dynamics, and cell-to-cell fusion. These processes, in turn, enable larger-scale biological functions, including fertilization, tissue development, and body movement.

In the Membrane Remodeling Lab, we use membrane remodeling as a lens to study how cells build, maintain, and adapt their composition, architecture, and function. We are especially interested in systems that operate at extreme scales or levels of complexity, such as skeletal muscle fibers and large secretory vesicles. By studying these systems, we aim to uncover new concepts and mechanisms that explain how membranes support cellular function, tissue organization, and organismal physiology.

To address these questions, we combine genetics, biochemistry, cell biology, and multimodal imaging, including advanced live-cell microscopy and three-dimensional correlative light and electron microscopy. Our models span cultured cells, flies, and mice, allowing us to connect molecular mechanisms to their physiological roles in tissue morphogenesis, homeostasis, and regeneration.

Our research has uncovered molecular and mechanistic adaptations that allow giant secretory vesicles to release cargo efficiently without overwhelming the cell surface, as well as signaling pathways that regulate cell fusion during regenerative myogenesis. Building on these insights, we are now exploring how organelles reorganize during muscle development, growth, repair, and regeneration, and how muscle stem cells fuse with mature muscle fibers during myonuclear accretion in response to physiological cues such as exercise.

By studying membrane dynamics across temporal and physical scales, we aim to reveal general principles that link cellular architecture, tissue function, and disease.

Research page

Regulation of Membrane Fusion

Organelle Trafficking and Remodeling

Latest Publications

Cyclosporine A rescues the influenza virus fusion with IFITM3-expressing cells by relocating the restriction factor to intraluminal vesicles of multivesicular bodies

Buth S. A., Marin M., Zhang Y., Avinoam O. & Melikyan G. B. (2026) Journal of Virology. 100, 4, e0204525.

Interferon-induced transmembrane protein 3 (IFITM3) blocks fusion of many enveloped viruses with endosomes, likely by rigidifying the cell membrane. We and others have previously reported that cyclosporine A (CsA) treatment rescues the ability of the influenza A virus (IAV) to fuse with and infect IFITM3-expressing cells, but the mechanism of such rescue remained controversial. Here, we employed correlative light-electron microscopy (CLEM) and on-section electron tomography workflow to visualize the IAV fusion intermediates arrested by IFITM3. Most common intermediates were tight IAV contacts with the limiting membrane and intraluminal vesicles of late endosomes. A hemifusion intermediate was also detected. We further visualized the effect of CsA on IFITM3 localization by immunoelectron microscopy (immuno-EM), which revealed a marked relocation of IFITM3 from the limiting membrane to intraluminal vesicles of endosomes. This CsA-induced IFITM3 sequestration in intraluminal vesicles likely relieves the block for IAV fusion with the limiting membrane of endosomes that culminates in a release of the viral nucleoprotein complex into the cytoplasm.

Visualizing suborganellar lipid distribution using correlative light and electron microscopy

Lennartz H. M., Khan S., Leng W., Böhlig K., Fabig G., Kieswald Y., Elsner F., Scher N., Wilsch-Bräuninger M., Avinoam O. & Nadler A. (2026) Nature Cell Biology.

Lipids and proteins compartmentalize biological membranes into nanoscale domains, which are crucial for signalling, intracellular trafficking and many other cellular processes. Studying nanodomain function requires the ability to measure protein and lipid localization at the nanoscale. Current methods for visualizing lipid localization do not meet this requirement. Here we introduce a correlative light and electron microscopy workflow to image lipids (Lipid-CLEM), combining near-native lipid probes and on-section labelling by click chemistry. This approach enables the quantification of relative lipid densities in membrane nanodomains. We find differential partitioning of sphingomyelin into intraluminal vesicles, recycling tubules and the boundary membrane of the early endosome, representing a degree of nanoscale organization previously observed only for proteins. We anticipate that our Lipid-CLEM workflow will greatly facilitate the mechanistic analysis of lipid functions in cell biology, allowing for the simultaneous investigation of proteins and lipids during membrane nanodomain assembly and function.

A versatile GPMV-imaging platform for quantitative analysis of receptor binding and membrane fusion

Yosibash I., Khan S., Vaknin A., Dharan R., Lichtenstein A., Golani G., Daniel S., Avinoam O. & Sorkin R. (2026) Biophysical Journal. 125, 1, p. 294-304

Membrane fusion is central to biological processes such as viral entry, fertilization, and cell-to-cell fusion. Gaining a mechanistic understanding of fusion requires the ability to visualize and quantify the dynamic interaction between two membranes and their associated protein machineries at high temporal and spatial resolution. However, studying these processes in live cells remains challenging due to the complexity of the cellular environment. Here, we demonstrate a versatile cell-free platform based on giant plasma membrane vesicles that enables controlled, quantitative analysis of receptor binding and membrane fusion kinetics in a native membrane context. As proof of concept, we reconstitute the SARS-CoV-1 Spike-ACE2 interaction, capturing specific receptor engagement and accumulation at the membrane interface using confocal microscopy and micropipette aspiration. Fusion was induced by proteolytic activation and quantified using both high-resolution microscopy and high-throughput imaging flow cytometry. The platform also reveals the influence of membrane composition on fusion efficiency, demonstrated by the impact of cholesterol depletion. This approach provides a broadly applicable system for dissecting membrane fusion and protein-protein interactions across membranes, with compatibility for biophysical, imaging, and structural analysis. It offers new opportunities for mechanistic studies and inhibitor screening in a biologically relevant yet experimentally accessible context.

All Publications