title: The role of cholesterol-sphingomyelin membrane nanodomains in the stability of intercellular membrane nanotubes.
abstract: Intercellular membrane nanotubes (ICNs) are highly curved tubular structures that connect neighboring cells. The stability of these structures depends on the inner cytoskeleton and the cell membrane composition. Yet, due to the difficulty in the extraction of ICNs, the cell membrane composition remains elusive. In the present study, a raft marker, ostreolysin, revealed the enrichment of cholesterol-sphingomyelin membrane nanodomains along ICNs in a T24 (malignant) urothelial cancer cell line. Cholesterol depletion, due to the addition of methyl-β-cyclodextrin, caused the dispersion of cholesterol-sphingomyelin membrane nanodomains and the retraction of ICNs. The depletion of cholesterol also led to cytoskeleton reorganization and to formation of actin stress fibers. Live cell imaging data revealed the possible functional coupling between the change from polygonal to spherical shape, cell separation, and the disconnection of ICNs. The ICN was modeled as an axisymmetric tubular structure, enabling us to investigate the effects of cholesterol content on the ICN curvature. The removal of cholesterol was predicted to reduce the positive spontaneous curvature of the remaining membrane components, increasing their curvature mismatch with the tube curvature. The mechanisms by which the increased curvature mismatch could contribute to the disconnection of ICNs are discussed.
authors.affiliation: Laboratory of Biophysics, Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Maruša
authors.initials: M
authors.lastname: Lokar
authors.forename: Doron
authors.initials: D
authors.lastname: Kabaso
authors.forename: Nataša
authors.initials: N
authors.lastname: Resnik
authors.forename: Kristina
authors.initials: K
authors.lastname: Sepčić
authors.forename: Veronika
authors.initials: V
authors.lastname: Kralj-Iglič
authors.forename: Peter
authors.initials: P
authors.lastname: Veranič
authors.forename: Robert
authors.initials: R
authors.lastname: Zorec
authors.forename: Aleš
authors.initials: A
authors.lastname: Iglič
mesh_terms: D045744:Cell Line, Tumor; D048430:Cell Shape / Q000502:physiology; D002784:Cholesterol / Q000737:chemistry*; D003470:Culture Media / Q000737:chemistry; D005110:Extracellular Space / Q000737:chemistry; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D013109:Sphingomyelins / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003470:Culture Media; D013109:Sphingomyelins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol