Alexander B. Verkhovsky

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While the protrusive event of cell locomotion is thought to be driven by actin polymerization, the mechanism of forward translocation of the cell body is unclear. To elucidate the mechanism of cell body translocation, we analyzed the supramolecular organization of the actin-myosin II system and the dynamics of myosin II in fish epidermal keratocytes. In(More)
BACKGROUND Directional cell motility implies the presence of a steering mechanism and a functional asymmetry between the front and rear of the cell. How this functional asymmetry arises and is maintained during cell locomotion is, however, unclear. Lamellar fragments of fish epidermal keratocytes, which lack nuclei, microtubules and most organelles, present(More)
We have developed an improved electron microscopic procedure appropriate for correlative light and electron microscopy of the cytoskeleton. The procedure is based on detergent extraction, chemical fixation, critical point drying, and platinum/carbon coating of cultured cells and the improvements consist of modifications which are minor individually but(More)
Leading edge protrusion is one of the critical events in the cell motility cycle and it is believed to be driven by the assembly of the actin network. The concept of dendritic nucleation of actin filaments provides a basis for understanding the organization and dynamics of the actin network at the molecular level. At a larger scale, the dynamic geometry of(More)
Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs), and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow), and the lamellum (zone of slow flow located between the lamellipodium and the cell body).(More)
The morphogenesis of myosin II structures in active lamella undergoing net protrusion was analyzed by correlative fluorescence and electron microscopy. In rat embryo fibroblasts (REF 52) microinjected with tetramethylrhodamine-myosin II, nascent myosin spots formed close to the active edge during periods of retraction and then elongated into wavy ribbons of(More)
The organization of myosin in the fibroblast lamellum was studied by correlative fluorescence and electron microscopy after a novel procedure to reveal its underlying morphology. An X-rhodamine analog of conventional smooth muscle myosin (myosin II) that colocalized after microinjection with endogenous myosin was used to trace myosin distribution in living(More)
The lamellipod, the locomotory region of migratory cells, is shaped by the balance of protrusion and contraction. The latter is the result of myosin-generated centripetal flow of the viscoelastic actin network. Recently, quantitative flow data was obtained, yet there is no detailed theory explaining the flow in a realistic geometry. We introduce models of(More)
Kinetic and structural analysis of the actin-myosin II system in mammalian fibroblasts and fish epidermal keratocytes suggests that the cell's motility machinery arises behind the leading edge in the form of myosin filament clusters immersed in an actin filament network. We discuss how the contraction of this actin-myosin II network is related to the(More)
Initial integrin-mediated cell-matrix adhesions (focal complexes) appear underneath the lamellipodia, in the regions of the "fast" centripetal flow driven by actin polymerization. Once formed, these adhesions convert the flow behind them into a "slow", myosin II-driven mode. Some focal complexes then turn into elongated focal adhesions (FAs) associated with(More)