Electrostatic cell-surface repulsion initiates lumen formation in developing blood vessels.
Blood vessels function in the uptake, transport, and delivery of gases and nutrients within the body. A key question is how the central lumen of blood vessels develops within a cord of vascular endothelial cells. Here, we demonstrate that sialic acids of apical glycoproteins localize to apposing endothelial cell surfaces and generate repelling electrostatic fields within an endothelial cell cord. Both in vitro and in vivo experiments show that the negative charge of sialic acids is required for the separation of endothelial cell surfaces and subsequent lumen formation. We also demonstrate that sulfate residues can substitute for sialic acids during lumen initiation. These results therefore reveal a key step in the creation of blood vessels, the most abundant conduits in the vertebrate body. Because negatively charged mucins and proteoglycans are often found on luminal cell surfaces, it is possible that electrostatic repulsion is a general principle also used to initiate lumen formation in other organs.
Institute of Metabolic Physiology, Heinrich-Heine-University of Düsseldorf, D-40225 Düsseldorf, Germany.
Boris
B
Strilić
Jan
J
Eglinger
Michael
M
Krieg
Martin
M
Zeeb
Jennifer
J
Axnick
Pavel
P
Babál
Daniel J
DJ
Müller
Eckhard
E
Lammert
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D055672:Static Electricity; D013499:Surface Properties
D019158:N-Acetylneuraminic Acid