Coupling of cytoskeleton functions for fibroblast locomotion.

Using a chick cell phenotype specialised for locomotion with morphometric measurements made possible by modern instrumentation technology, we have reinvestigated motile functions in fibroblast locomotion. Quantitative analysis of rapid fluctuations in cell form and organelle distribution during locomotion showed many significant correlations between different parts of the cell despite much irregularity in individual displacements over the time scale of the order of one second. These broke down when external perturbations caused changes in shape or direction. Partial energy deprivation caused the cells to lose control of shape and organelle distribution even though forward protrusion continued unaffected. Cytoplasmic displacements shown by marker mitochondria correlated with adjacent fluctuations at the leading edge, and drug treatments which increased the amplitude of mitochondrial movements caused visible protrusions in projected positions at the leading edge. We conclude that fibroblast locomotion may be driven coordinately by a common set of motility mechanisms and that this coordination may be lost as a result of physical or pharmacological disturbance. Taking our evidence with results from other Laboratories, we propose the following cytoskeleton functions. (i) Protrusive activity, probably based on solation--gelation cycles of the actin based cytoskeleton and membrane recycling which provides cellular and membrane components for streaming through the cell body to the leading edge; this is Ca++ sensitive but relatively energy insensitive. (ii) Constraining activity on the cell membrane and on certain organelles to maintain shape and so facilitate directionality and the drawing along of the trailing body; this is Ca++ insensitive but relatively energy sensitive. (iii) Channeling function of microtubules to direct the flow towards multiple foci on the leading edge, and so determine cell polarity. Such a mechanism of locomotion for fibroblasts has many features consistent with evidence for other cell types, especially amoebae and leukocytes.