Nano- and Microtubes: Tiny Fusion Events but Not Overall Plasma Membrane Merger for Exchanging Intracellular...

Membrane nanotubes, including tunneling nanotubes (TNTs), tumor microtubes (TMs), cytonemes, and related structures, constitute open-ended conduits that directly connect cells. They enable the directed exchange of organelles, nucleic acids, proteins, and ions across tens to hundreds of micrometers while preserving cellular identities. Specifically, this chapter synthesizes the current understanding of mechanisms, delineates cargo selectivity and transfer modes, and integrates cancer-relevant functions, such as mitochondrial transfer, calcium-wave propagation, and therapy adaptation. We emphasize rigorous criteria and multimodal workflows to distinguish conduit-mediated exchange from gap junction coupling, extracellular vesicles (EVs), trogocytosis, entosis, and bona fide cell-cell fusion. Across carcinomas and malignancies, tubes organize multicellular networks that distribute stress, shape metabolic plasticity, and seed resistant subclones. We outline vulnerabilities in tube biogenesis and coupling, propose a communication-fusion continuum, and set near-term priorities for in vivo quantification and translational targeting.