title: Atomic force microscopy study of early morphological changes during apoptosis.
abstract: 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.
authors.affiliation: Department of Chemistry, and the Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109-1055, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hessler
authors.forename: Andrew
authors.initials: A
authors.lastname: Budor
authors.forename: Krishna
authors.initials: K
authors.lastname: Putchakayala
authors.forename: Almut
authors.initials: A
authors.lastname: Mecke
authors.forename: Daniel
authors.initials: D
authors.lastname: Rieger
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
authors.forename: Anna
authors.initials: A
authors.lastname: Bielinska
authors.forename: James
authors.initials: J
authors.lastname: Beals
authors.forename: James
authors.initials: J
authors.lastname: Baker
mesh_terms: 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
chemical_list: D010718:Phosphatidylserines