Researchers discover how cellular membranes change curvature depending on BAR proteins

A team of researchers at IBEC and UPC, led by Pere Roca-Cusachs and Marino Arroyo, study how BAR proteins, a family of molecules that bind curved cellular membranes, reshape these membranes. Scientists report in the journal Nature Communications, through both experiments and modelling, the dynamics of these membrane reshaping processes that occur both in normal cells or disease scenarios.

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Simulations of a membrane tube (600nm diameter) dynamically reshaped by a BAR protein.

The human body is a complex mosaic made up of a very large number of cells with different properties, but they all share a common feature: they possess an external envelope (also called membrane), which is curved at the micrometer and nanometer scales.

During essential cell functions like migration, endo/exocytosis, or when they are deformed by external forces, cell membranes constantly change shape. Here, BAR proteins play a fundamental role. However, the dynamics and mechanochemistry of the process was not well understood until now.

Now, a group of researchers at the Institute for Bioengineering of Catalonia (IBEC) and at the Polytechnical University of Catalonia (UPC) publish new results in the Journal Nature Communications, providing a foundation to understand several processes of membrane deformation, that occur both in normal cell physiology and in disease scenarios. Specifically, researchers describe novel reshaping events of low-curvature membrane structures by BAR proteins, which were previously not considered. Researchers also show how mechanically deforming the membrane triggers a biochemical response mediated by BAR proteins.

The key to understand cell membranes and their curvature 

Experimentally, researchers developed an in vitro system to mechanically deform artificial membranes, expose them to purified BAR proteins, and observed the resulting dynamics by confocal microscopy. In addition, researchers developed theoretical models to understand the process, capturing the dynamics and mechanochemistry of the process. Combining both, experimental and theoretical approaches, researchers also observed that cell membrane deformations depend on initial membrane shape.

Anabel-Lise le Roux (IBEC) and Caterina Tozzi (UPC), co-first authors of the study, explain the importance of having both experimental and theoretical approaches to understand such complex deformation processes.

“The really tight interaction between experiments and modelling was essential to deeply understand a very complex mechanochemical process”.
Anabel-Lise Le Roux and Caterina Tozzi.

The work published in Nature Communications was senior-authored by Marino Arroyo (UPC) and Pere Roca-Cusachs (IBEC/UB).

 

Reference article: Anabel-Lise Le Roux, Caterina Tozzi, Nikhil Walani , Xarxa Quiroga, Dobryna Zalvidea, Xavier Trepat, Margarita Staykova, Marino Arroyo, Pere Roca-Cusachs. Dynamic Mechanochemical feedback between curved membranes and BAR protein self-organization. Nat Commun 12, 6550 (2021).