title: Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?
abstract: Nonlamellar lipid arrangements, including cubosomes, appear in unhealthy cells, e.g., when they are subject to stress, starvation, or viral infection. The bioactivity of cubosomes-nanoscale particles exhibiting bicontinuous cubic structures-versus more common vesicles is an unexplored area due to lack of suitable model systems. Here, glycodendrimercubosomes (GDCs)-sugar-presenting cubosomes assembled from Janus glycodendrimers by simple injection into buffer-are proposed as mimics of biological cubic membranes. The bicontinuous cubic GDC architecture has been demonstrated by electron tomography. The stability of these GDCs in buffer enabled studies on lectin-dependent agglutination, revealing significant differences compared with the vesicular glycodendrimersome (GDS) counterpart. In particular, GDCs showed an increased activity toward concanavalin A, as well as an increased sensitivity and selectivity toward two variants of banana lectins, a wild-type and a genetically modified variant, which is not exhibited by GDSs. These results suggest that cells may adapt under unhealthy conditions by undergoing a transformation from lamellar to cubic membranes as a method of defense.
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6321, United States.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Electron Microscopy Resource Laboratory, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6082, United States.
authors.forename: Dewight
authors.initials: D
authors.lastname: Williams
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Pawaret
authors.initials: P
authors.lastname: Leowanawat
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Mihai
authors.initials: M
authors.lastname: Peterca
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Sherman
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6321, United States; Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6391, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.affiliation: Department of Physics and Astronomy, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6396, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heiney
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Program in Immunology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: King
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Program in Immunology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University , Veterinärstrasse 13, 80539 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University , Veterinärstrasse 13, 80539 Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Institute of Computational Molecular Science, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Virgil
authors.initials: V
authors.lastname: Percec