Atomic force microscopy study of early morphological changes during apoptosis.
Apoptosis is defined by a distinct set of morphological changes observed during cell death including loss of focal adhesions, the formation of cell membrane buds or blebs, and a decrease in total cell volume. Recent studies suggest that these dramatic morphological changes, particularly apoptotic volume decrease (AVD), are an early prerequisite to apoptosis and precede key biochemical time-points. Here we use atomic force microscopy to observe early stage AVD of KB cells undergoing staurosporine-induced apoptosis. After a 3-h exposure to 1 microM staurosporine, a 32% decrease in total cell height and a 50% loss of total cell volume is observed accompanied by only a 15% change in cell diameter. The observed AVD precedes key biochemical hallmarks of apoptosis such as loss of mitochondrial membrane potential, phosphatidyl serine translocation, nuclear fragmentation, and measurable caspase-3 activity. This suggests that morphological volume changes occur very early in the induction of apoptosis.
Hessler
Jessica A
JA
Department of Chemistry, and the Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Budor
Andrew
A
Putchakayala
Krishna
K
Mecke
Almut
A
Rieger
Daniel
D
Banaszak Holl
Mark M
MM
Orr
Bradford G
BG
Bielinska
Anna
A
Beals
James
J
Baker
James
J
D017209:Apoptosis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure*; D048429:Cell Size; D006801:Humans; D007624:KB Cells / Q000378:metabolism / Q000648:ultrastructure*; D018625:Microscopy, Atomic Force / Q000379:methods*; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D010718:Phosphatidylserines / Q000378:metabolism; D013997:Time Factors
D010718:Phosphatidylserines