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Oleg Y. Chaga

Bio: Oleg Y. Chaga is an academic researcher from Northwestern University. The author has contributed to research in topics: Lamellipodium & Filopodia. The author has an hindex of 9, co-authored 9 publications receiving 2736 citations.

Papers
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Journal ArticleDOI
17 May 2002-Cell
TL;DR: It is concluded that Ena/VASP regulates cell motility by controlling the geometry of actin filament networks within lamellipodia.

850 citations

Journal ArticleDOI
TL;DR: A convergent elongation model of filopodia initiation is proposed, stipulating that filaments within the lamellipodial dendritic network acquire privileged status by binding a set of molecules (including VASP) to their barbed ends, which protect them from capping and mediate association of barbed Ends with each other.
Abstract: Afilopodium protrudes by elongation of bundled actin filaments in its core. However, the mechanism of filopodia initiation remains unknown. Using live-cell imaging with GFP-tagged proteins and correlative electron microscopy, we performed a kinetic-structural analysis of filopodial initiation in B16F1 melanoma cells. Filopodial bundles arose not by a specific nucleation event, but by reorganization of the lamellipodial dendritic network analogous to fusion of established filopodia but occurring at the level of individual filaments. Subsets of independently nucleated lamellipodial filaments elongated and gradually associated with each other at their barbed ends, leading to formation of cone-shaped structures that we term Λ-precursors. An early marker of initiation was the gradual coalescence of GFP-vasodilator-stimulated phosphoprotein (GFP-VASP) fluorescence at the leading edge into discrete foci. The GFP-VASP foci were associated with Λ-precursors, whereas Arp2/3 was not. Subsequent recruitment of fascin to the clustered barbed ends of Λ-precursors initiated filament bundling and completed formation of the nascent filopodium. We propose a convergent elongation model of filopodia initiation, stipulating that filaments within the lamellipodial dendritic network acquire privileged status by binding a set of molecules (including VASP) to their barbed ends, which protect them from capping and mediate association of barbed ends with each other.

773 citations

Journal ArticleDOI
09 Feb 2007-Cell
TL;DR: Actin polymerization periodically builds a mechanical link, the lamellipodium, connecting myosin motors with the initiation of adhesion sites, suggesting that the major functions driving motility are coordinated by a biomechanical process.

513 citations

Journal ArticleDOI
TL;DR: This article demonstrates that random motions of motile cells can be rectified by asymmetric (‘ratchet’) microgeometries and observations that the direction of preferred motion can be different for different species of cell are provided.
Abstract: Cell motility is a process deriving from the synchronized dynamics of the cytoskeleton. In several important physiological processes—notably, cancer metastasis—the randomly moving cells can acquire a directional motility phenotype and bias their motions in response to environmental cues. Despite intense research, however, the current understanding of directional cell migration is incomplete and there is a growing need to develop systems that would enable the study and control of this process. This article demonstrates that random motions of motile cells can be rectified by asymmetric (‘ratchet’) microgeometries. Interactions between the cells and the imposed geometrical cues guide cell polarization and give rise to directional motility. Depending on the ratchet design, cells of different types can move either in the same or in opposite directions on the same imposed pattern. In the latter case, it is possible to partially sort mixed cell populations into different collecting reservoirs. It is not surprising that a microfluidic channel whose walls have a ratchet-like structure can preferentially direct the flow of large particles in one direction. But a study of the movement of living cells through such channels provides the remarkable observation that the direction of preferred motion can be different for different species of cell.

282 citations

Journal ArticleDOI
TL;DR: Rickettsia use an Arp2/3 complex‐dependent actin‐nucleation mechanism similar to that of other pathogens, and it is proposed that additional Rickettsia or host factors reorganize the Y‐branched networks into parallel arrays in a manner similar to a recently proposed model of filopodia formation.
Abstract: Summary Spotted fever group Rickettsia are obligate intracellu- lar pathogens that exploit the host cell actin cytosk- eleton to promote motility and cell-to-cell spread. Although other pathogens such as Listeria monocy- togenes use an Arp2/3 complex-dependent nucleation mechanism to generate comet tails consisting of Y- branched filament arrays, Rickettsia polymerize tails consisting of unbranched filaments by a previously unknown mechanism. We identified genes in several Rickettsia species encoding proteins (termed RickA) with similarity to the WASP family of Arp2/3-complex activators. Rickettsia rickettsii RickA activated both the nucleation and Y-branching activities of the Arp2/ 3 complex like other WASP-family proteins, and was sufficient to direct the motility of microscopic beads in cell extracts. Actin tails generated by RickA-coated beads consisted of Y-branched filament networks. These data suggest that Rickettsia use an Arp2/3 com- plex-dependent actin-nucleation mechanism similar to that of other pathogens. We propose that additional Rickettsia or host factors reorganize the Y-branched networks into parallel arrays in a manner similar to a recently proposed model of filopodia formation.

145 citations


Cited by
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Journal ArticleDOI
21 Feb 2003-Cell
TL;DR: A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion.

3,793 citations

Journal ArticleDOI
TL;DR: This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.
Abstract: Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.

2,876 citations

Journal ArticleDOI
28 Jan 2010-Nature
TL;DR: An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.
Abstract: The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.

2,323 citations

Journal ArticleDOI
TL;DR: The mechanisms of such environmental sensing are discussed, based on the finely tuned crosstalk between the assembly of one type of integrin-based adhesion complex, namely focal adhesions, and the forces that are at work in the associated cytoskeletal network owing to actin polymerization and actomyosin contraction.
Abstract: Recent progress in the design and application of artificial cellular microenvironments and nanoenvironments has revealed the extraordinary ability of cells to adjust their cytoskeletal organization, and hence their shape and motility, to minute changes in their immediate surroundings. Integrin-based adhesion complexes, which are tightly associated with the actin cytoskeleton, comprise the cellular machinery that recognizes not only the biochemical diversity of the extracellular neighbourhood, but also its physical and topographical characteristics, such as pliability, dimensionality and ligand spacing. Here, we discuss the mechanisms of such environmental sensing, based on the finely tuned crosstalk between the assembly of one type of integrin-based adhesion complex, namely focal adhesions, and the forces that are at work in the associated cytoskeletal network owing to actin polymerization and actomyosin contraction.

2,322 citations

Journal ArticleDOI
TL;DR: In this article, the authors provide a guided tour through the development of artificial self-propelling microparticles and nanoparticles and their application to the study of nonequilibrium phenomena, as well as the open challenges that the field is currently facing.
Abstract: Differently from passive Brownian particles, active particles, also known as self-propelled Brownian particles or microswimmers and nanoswimmers, are capable of taking up energy from their environment and converting it into directed motion. Because of this constant flow of energy, their behavior can be explained and understood only within the framework of nonequilibrium physics. In the biological realm, many cells perform directed motion, for example, as a way to browse for nutrients or to avoid toxins. Inspired by these motile microorganisms, researchers have been developing artificial particles that feature similar swimming behaviors based on different mechanisms. These man-made micromachines and nanomachines hold a great potential as autonomous agents for health care, sustainability, and security applications. With a focus on the basic physical features of the interactions of self-propelled Brownian particles with a crowded and complex environment, this comprehensive review will provide a guided tour through its basic principles, the development of artificial self-propelling microparticles and nanoparticles, and their application to the study of nonequilibrium phenomena, as well as the open challenges that the field is currently facing.

2,188 citations