Mechanical dynamics of single cells during early apoptosis.
Dynamic mechanical properties of cells are becoming recognized as indicators and regulators of physiological processes such as differentiation, malignant phenotypes and mitosis. A key process in development and homeostasis is apoptosis and whilst the molecular control over this pathway is well studied, little is known about the mechanical consequences of cell death. Here, we study the caspase-dependent mechanical kinetics of single cells during early apoptosis initiated with the general protein-kinase inhibitor staurosporine. This results in internal remodelling of the cytoskeleton and nucleus which is reflected in dynamic changes in the mechanical properties of the cell. Utilizing simultaneous confocal and atomic force microscopy (AFM), we measured distinct mechanical dynamics in the instantaneous cellular Young's Modulus and longer timescale viscous deformation. This allowed us to visualize time-dependent nuclear and cytoskeletal control of force dissipation with fluorescent fusion proteins throughout the cell. This work reveals that the cell death program not only orchestrates biochemical dynamics but also controls the mechanical breakdown of the cell. Importantly, the consequences of mechanical disregulation during apoptosis may be a contributing factor to several human pathologies through the poorly timed release of dead cells and cell debris.
Pelling
Andrew E
AE
Centre for Nanomedicine, The London Centre for Nanotechnology, University College London, London, United Kingdom. a@pellinglab.net
Veraitch
Farlan S
FS
Chu
Carol Pui-Kei
CP
Mason
Chris
C
Horton
Michael A
MA
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D034904:Lamin Type A / Q000187:drug effects / Q000378:metabolism; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D015739:Nocodazole / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013314:Stress, Mechanical; D014162:Transfection; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
D000199:Actins; D004791:Enzyme Inhibitors; D034904:Lamin Type A; D019384:Nucleic Acid Synthesis Inhibitors; D014404:Tubulin; D050257:Tubulin Modulators; D015638:Cytochalasin D; D019311:Staurosporine; D015739:Nocodazole