Self-polarization and directional motility of cytoplasm

Background: Directional cell motility implies the presence of a steering me chanism and a functional asymmetry between the front and rear of the cell. How this functional asymmetry arises and is maintained during cell locomoti on is, however, unclear. Lamellar fragments of fish epidermal keratocytes, which lack nuclei, microtubules and most organelles, present a simplified, perhaps minimal, system for analyzing this problem because they consist of little other than the motile machinery enclosed by a membrane and yet can m ove with remarkable speed and persistence. Results: We have produced two types of cellular fragments: discoid stationa ry fragments and polarized fragments undergoing locomotion. The organizatio n and dynamics of the actin-myosin II system were isotropic in stationary f ragments and anisotropic in the moving fragments. To investigate whether th e creation of asymmetry could result in locomotion, a transient mechanical stimulus was applied to stationary fragments. The stimulus induced localize d contraction and the formation of an actin-myosin II bundle at one edge of the fragment. Remarkably, stimulated fragments started to undergo locomoti on and the locomotion and associated anisotropic organization of the actin- myosin II system were sustained after withdrawal of the stimulus. Conclusions: We propose a model in which lamellar cytoplasm is considered a dynamically bistable system capable of existing in a non-polarized or pola rized state and interconvertible by mechanical stimulus. The model explains how the anisotropic organization of the lamellum is maintained in the proc ess of locomotion. Polarized locomotion is sustained through a positive-fee dback loop intrinsic to the actin-myosin II machinery: anisotropic organiza tion of the machinery drives translocation, which then reinforces the asymm etry of the machinery, favoring further translocation.