Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2.

Autor: Junqueira Alves C, Hannah T, Sadia S, Kolsteeg C, Dixon A, Wiener RJ, Nguyen H, Tipping MJ, Ladeira JS, Franklin PFDC, Dutra de Nigro NP, Dias RA, Zabala Capriles PV, Rodrigues Furtado de Mendonça JP, Slesinger P, Costa K, Zou H, Friedel RH
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 02. Date of Electronic Publication: 2024 Jan 02.
DOI: 10.1101/2024.01.02.573660
Abstrakt: Glioblastoma (GBM) is a malignant brain tumor with uncontrolled invasive growth. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 to gain biomechanical plasticity for polarized migration through confined space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal active endocytosis at cell front and filamentous actin assembly at rear to propel GBM cells through constrictions. These two processes are interconnected and governed by Plexin-B2 that orchestrates cortical actin and membrane tension, shown by biomechanical assays. Molecular dynamics simulations predict that balanced membrane and actin tension are required for optimal migratory velocity and consistency. Furthermore, Plexin-B2 mechanosensitive function requires a bendable extracellular ring structure and affects membrane internalization, permeability, phospholipid composition, as well as inner membrane surface charge. Together, our studies unveil a key element of membrane tension and mechanoelectrical coupling via Plexin-B2 that enables GBM cells to adapt to physical constraints and achieve polarized confined migration.
Databáze: MEDLINE