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Title: Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?

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:
ORCiD logo [1] ;  [2] ;  [3] ;  [4] ; ORCiD logo [4] ;  [4] ;  [4] ;  [5] ;  [6] ;  [7] ;  [7] ;  [8] ;  [8] ;  [9] ; ORCiD logo [4]
  1. Univ. of Pennsylvania, Philadelphia, PA (United States). Roy & Diana Vagelos Laboratories, Department of Chemistry
  2. Univ. of Pennsylvania, Philadelphia, PA (United States). Department of Bioengineering
  3. Univ. of Pennsylvania, Philadelphia, PA (United States). Electron Microscopy Resource Laboratory, Department of Biochemistry and Biophysics, Perelman School of Medicine
  4. Univ. of Pennsylvania, Philadelphia, PA (United States). Roy & Diana Vagelos Laboratories, Department of Chemistry
  5. Univ. of Pennsylvania, Philadelphia, PA (United States). Department of Bioengineering and Department of Chemical and Biomolecular Engineering
  6. Univ. of Pennsylvania, Philadelphia, PA (United States). Department of Physics and Astronomy
  7. Univ. of Michigan, Ann Arbor, MI (United States). Division of Infectious Diseases, Department of Internal Medicine, Program in Immunology
  8. Ludwig-Maximilians-University, Munich (Germany). Institute of Physiological Chemistry, Faculty of Veterinary Medicine
  9. Temple University, Philadelphia, PA (United States). Institute of Computational Molecular Science
Publication Date:
Grant/Contract Number:
SC0007063
Type:
Accepted Manuscript
Journal Name:
ACS Central Science
Additional Journal Information:
Journal Volume: 2; Journal Issue: 12; Journal ID: ISSN 2374-7943
Publisher:
American Chemical Society (ACS)
Research Org:
Univ. of Pennsylvania, Philadelphia, PA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1425620

Xiao, Qi, Wang, Zhichun, Williams, Dewight, Leowanawat, Pawaret, Peterca, Mihai, Sherman, Samuel E., Zhang, Shaodong, Hammer, Daniel A., Heiney, Paul A., King, Steven R., Markovitz, David M., Andre, Sabine, Gabius, Hans-Joachim, Klein, Michael L., and Percec, Virgil. Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?. United States: N. p., Web. doi:10.1021/acscentsci.6b00284.
Xiao, Qi, Wang, Zhichun, Williams, Dewight, Leowanawat, Pawaret, Peterca, Mihai, Sherman, Samuel E., Zhang, Shaodong, Hammer, Daniel A., Heiney, Paul A., King, Steven R., Markovitz, David M., Andre, Sabine, Gabius, Hans-Joachim, Klein, Michael L., & Percec, Virgil. Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?. United States. doi:10.1021/acscentsci.6b00284.
Xiao, Qi, Wang, Zhichun, Williams, Dewight, Leowanawat, Pawaret, Peterca, Mihai, Sherman, Samuel E., Zhang, Shaodong, Hammer, Daniel A., Heiney, Paul A., King, Steven R., Markovitz, David M., Andre, Sabine, Gabius, Hans-Joachim, Klein, Michael L., and Percec, Virgil. 2016. "Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?". United States. doi:10.1021/acscentsci.6b00284. https://www.osti.gov/servlets/purl/1425620.
@article{osti_1425620,
title = {Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?},
author = {Xiao, Qi and Wang, Zhichun and Williams, Dewight and Leowanawat, Pawaret and Peterca, Mihai and Sherman, Samuel E. and Zhang, Shaodong and Hammer, Daniel A. and Heiney, Paul A. and King, Steven R. and Markovitz, David M. and Andre, Sabine and Gabius, Hans-Joachim and Klein, Michael L. and Percec, Virgil},
abstractNote = {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.},
doi = {10.1021/acscentsci.6b00284},
journal = {ACS Central Science},
number = 12,
volume = 2,
place = {United States},
year = {2016},
month = {12}
}