Apoptosis of syncytia induced by the HIV-1-envelope glycoprotein complex: Influence of cell shape and size

Cells stably transfected with a lymphotropic HIV-1 Env gene form syncytia w hen cocultured with CD4(+)CXCR4(+) cells. Heterokaryons then spontaneously undergo apoptosis, while manifesting signs of mitochondrial membrane pemeab ilization as well as nuclear chromatin condensation. Modulation of cellular geometry was achieved by growing syncytia on self-assembled monolayers of terminally substituted alkanethiolates designed to control the adhesive pro perties of the substrates, Spreading of syncytia, induced by culturing them on small circular adhesive islets (diameter 5 mum), placed at a distance t hat cells can bridge (10 mum), inhibited spontaneous and staurosporin-induc ed signs of apoptosis, both at the mitochondrial and at the nuclear levels, and allowed for the generation of larger syncytia, Transient cell spreadin g conferred a memory of apoptosis inhibition which was conserved upon adopt ion of a conventional cell shape. Limiting syncytium size by culturing them on square-shaped planar adhesive islands of defined size (400 to 2500 E mu m(2)), separated by nonadhesive regions, enhanced the rate of apoptotic cel l death, as indicated by an accelerated permeabilization of the outer mitoc hondrial membrane, loss of the mitochondrial inner transmembrane potential, and an increased frequency of nuclear apoptosis. In conclusion, external c onstraints on syncytial size and shape strongly modulate their propensity t o undergo apoptosis. (C) 2000 Academic Press.