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bioRxiv · 10.64898/2026.08.10.743838

Emergence of tunneling nanotube-like intervesicular connections

Park, S. H.·Lee, S. H.·Kim, C. H.·Yin, C.·Xue, K.·Tian, L.·Shin, K.
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Abstract

Tunneling nanotubes (TNTs) are actin-supported membrane bridges that mediate long-range intercellular communication and direct transfer of signaling molecules, organelles, and pathogenic cargo, yet the physicochemical mechanisms underlying their formation and organization remain poorly understood. Here we show that TNT-like intervesicular connections emerge from minimal physicochemical interactions between actin filaments and lipid membranes. Upon Mg2+ exposure, actin-encapsulating vesicles spontaneously generated actin bundle-embedded lipid nanotubes (AT-LNTs) that formed stable intervesicular networks. Mg2+ simultaneously induced actin polymerization, filament bundling, and electrostatic recruitment of F-actin to phosphatidylcholine membranes, enabling membrane tubulation without actin-binding proteins. Systematic perturbation of membrane phase, membrane tension, Mg2+ concentration, ionic strength, and actin concentration revealed that AT-LNT formation occurs only within a narrow physicochemical regime where membrane deformation and actin-membrane coupling are simultaneously permissive. The resulting AT-LNTs reproduced key structural and dynamic features of cellular TNTs, including bundled organization, helical unwinding, lumenal diffusion, and spontaneous bridging between synthetic vesicles and living cells. These findings establish a minimal biophysical framework for understanding the emergence of intercellular membrane connections in living systems and provide a foundation for engineering communication between synthetic and living cell.

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Park, S. H., Lee, S. H., Kim, C. H., Yin, C., Xue, K., Tian, L., Shin, K.. 2026-08-11. Emergence of tunneling nanotube-like intervesicular connections. https://doi.org/10.64898/2026.08.10.743838

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