Formation principles of tunneling nanotubes

Tunneling nanotubes (TNTs) are thin membranous tubes that connect cells, providing a route for cell-to-cell communication and pathogen spread. TNTs form between a variety of cell types, but the mechanisms by which they form are largely unknown. We review general concepts related to the formation and stability of membranous tubular structures, with a focus on a membrane nanodomain deviatoric elasticity model. We examine experimental evidence that tubular structures form as a result of local membrane bending aided by laterally distributed proteins or anisotropic membrane nanodomains. The numerical results of several theoretical and simulation models of nanodomain segregation that suggest mechanisms of TNT inception and stability are also discussed. We address the relationship between the segregation of nanodomains and the protruding cytoskeletal forces, which are primarily produced in eukaryotic cells by the polymerization of actin. We also review the latest cell biological processes for the origin of TNTs in association with motor proteins in normal and cancer cells.