and time to accomplish essential cell processes. In thesame way that whole animal physical output requires the integration of the musculoskeletal, nervous, andcirculatory systems, whole cell physical outputs require the integration of specific subcellular machines. Clearlycertain subcellular machines will have central roles, while other machines may provide essential regulation orsupport. The relative contribution of different subcellular machines and how they are integrated to producephysical output has never been explored. Further, how the interactions between machines change to mediateadaptation, specialization or disease is completely unknown. At the single cell level, machines consist of organelle systems made up of small numbers to millions ofprotein and lipid molecules. Those that contribute to the structural and mechanical organization of the cell areprimarily the membrane systems and the cytoskeleton. The membrane systems allow for compartmentalizationof function. The cytoskeleton provides both a structural and directional framework to the cell. Decades of reductionist cell biology and biochemistry have produced a wealth of information about howindividual subcellular machines work. Molecular parts lists for many subcellular machines are in the range of50-100% complete. Standard assays for measuring the biochemical output of each machine are established.Targeted pharmacological, genetic or molecular perturbations exist to disrupt specific aspects of the function ofeach machine. With light microscopy it is possible to monitor changes in the dynamics of molecularcomponents within each machine from the large ensemble level down to the single molecule level. However,specific perturbation studies have almost singly been analyzed in terms of change in the
| Gupton, Stephanie L; Eisenmann, Kathryn; Alberts, Arthur S et al. (2007) mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. J Cell Sci 120:3475-87 |
