Cells have the ability to respond to various types of environmental cues, and in many cases these cues induce directed cell migration towards or away from these signals. How cells sense these cues and how they transmit that information to the cytoskeletal machinery governing cell translocation is one of the oldest and most challenging problems in biology. Chemotaxis, or migration towards diffusible chemical cues, has been studied for more than a century, but information is just now beginning to emerge about how cells respond to other cues, such as substrate-associated cues during haptotaxis (chemical cues on the surface), durotaxis (mechanical substrate compliance) and topotaxis (geometric features of substrate). Here we propose four common principles, or pillars, that underlie all forms of directed migration. First, a signal must be generated, a process that in physiological environments is much more nuanced than early studies suggested. Second, the signal must be sensed, sometimes by cell surface receptors, but also in ways that are not entirely clear, such as in the case of mechanical cues. Third, the signal has to be transmitted from the sensing modules to the machinery that executes the actual movement, a step that often requires amplification. Fourth, the signal has to be converted into the application of asymmetric force relative to the substrate, which involves mostly the cytoskeleton, but perhaps other players as well. Use of these four pillars has allowed us to compare some of the similarities between different types of directed migration, but also to highlight the remarkable diversity in the mechanisms that cells use to respond to different cues provided by their environment.

The cytoskeleton is composed of three distinct elements: actin microfilaments, microtubules and intermediate filaments. The actin cytoskeleton is thought to provide protrusive and contractile forces, and microtubules to form a polarized network allowing organelle and protein movement throughout the cell. Intermediate filaments are generally considered the most rigid component, responsible for the maintenance of the overall cell shape. Cytoskeletal elements must be coordinately regulated for the cell to fulfill complex cellular functions, as diverse as cell migration, cell adhesion and cell division. Coordination between cytoskeletal elements is achieved by signaling pathways, involving common regulators such as the Rho guanosine‐5′‐triphosphatases (GTPases). Furthermore, evidence is now accumulating that cytoskeletal elements participate in regulating each other. As a consequence, although their functions seem well defined, they are in fact overlapping, with actin playing a role in membrane trafficking and microtubules being involved in the control of protrusive and contractile forces. This cytoskeletal crosstalk is both direct and mediated by signaling molecules. Cell motility is a well‐studied example where the interplay between actin and microtubules appears bidirectional. This leads us to wonder which, if any, cytoskeletal element leads the way.

For many years, analyses of the role of the actomyosin cytoskeleton in many basic cellular processes have centered on actin. Increasingly, however, a number of investigators are examining proteins that are proximal to actin; in particular, nonmuscle myosin II (NMII). Recent experiments have increased our understanding of the role of NMII in three related cellular activities: generation of cell polarity, cell migration and cell-cell adhesion. Progress has been particularly promising thanks to the use of new microscopic, genetic and biochemical techniques. In mammalian systems, generation of transgenic mice and the introduction of specific siRNAs have been useful in deciphering the role of the three different isoforms of NMII: NMIIA, NMIIB and NMIIC. Studies in Drosophila and Aplysia, which are informative model systems for investigating the function of NMII, have also shed light on NMII. Recent work examines the contractile and structural roles that NMII plays at cell-cell boundaries, and both its contractile and actin-crosslinking roles in cell migration. In addition, NMII might also function as a scaffold molecule, anchoring signaling molecules, such as kinases and Rho GTPase guanine nucleotide exchange factors.

Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear. c-Abl tyrosine kinase plays a critical role in regulating actin dynamics and migration of airway smooth muscle cells and nonmuscle cells. Recent studies suggest that intermediate filaments undergo reorganization during migration, which coordinates focal adhesion dynamics, cell contraction, and nucleus rigidity. In particular, vimentin intermediate filaments undergo phosphorylation and reorientation in smooth muscle cells, which may regulate cell contraction and focal adhesion assembly/disassembly. Motile cells are characterized by a front-rear polarization of the microtubule framework, which regulates all essential processes leading to cell migration through its role in cell mechanics, intracellular trafficking, and signaling. This review recapitulates our current knowledge how the three cytoskeletal systems spatially and temporally modulate the migratory properties of cells. We also summarize the potential role of migration-associated biomolecules in lung and vascular diseases.

Cells utilize actin filaments to produce protrusive and contractile arrays that cooperate to drive cell motility. The generation of the two arrays and the coupling between them result from the unique properties of the lamellipodium, a protrusive leaflet of cytoplasm at the cell edge. From the lamellipodium into the lamella behind, there is a transition from a fast retrograde flow of actin polymer driven by polymerization to a slow flow driven by the interaction of anti-parallel arrays of actin with myosin. In addition to driving protrusion, the lamellipodium appears to play a role in supplying filaments to the lamella for the assembly of the contractile network required for traction.

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound by alpha-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated.

Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.

Dynamics of the cytoskeleton in Amoeba proteus. III. Influence of microinjected antibodies on the organization and function of the microfilament system. Affinity-purified antibodies against actin, myosin, alpha-actinin and vinculin cross-reacted with corresponding proteins from Amoeba proteus in immunoblotting experiments. Antibody staining of cells fixed during locomotion revealed different distribution patterns with a local concentration of anti-actin in the intermediate and of anti-myosin in the uroid region. Anti-alpha-actinin labeled a thin layer at the internal face of the plasma membrane, whereas anti-vinculin was distinctly concentrated at the base of advancing pseudopodia. Microinjection of different control solutions or antibodies against actin, myosin and alpha-actinin neither influenced the normal morphology and motile activity of amoebae nor changed the cellular distribution pattern of complementary antigens. However, antibodies against vinculin disorganized controlled locomotion and altered the spatial morphology of the microfilament system as well as the localization of the vinculin antigen thus pointing to a function of this protein in adhesion and locomotion of A.

Amoeboid movement Amoeboid movement is the most common type of movement in eukaryotic cells.[1] It is a crawling type of movement got by pushing out cell cytoplasm in the form of pseudopodia ("false feet"). The cytoplasm slides and forms a pseudopodium in front to move the cell forward. This type of movement is observed in amoebae, slime molds and some other protozoans such as Naegleria gruberi,[2] as well as some cells in humans such as white blood cells. Sarcomas, or cancers arising from connective tissue cells, are particularly good at amoeboid movement, thus leading to their high rate of metastasis. The exact mechanism is still unknown.[3][4] It involves actin-myosin molecules inside the cytoplasm. References - ↑ Nishigami, Yukinori; et al. (2013). "Reconstruction of active regular motion in Amoeba extract: dynamic cooperation between sol and gel states". PLOS ONE. 8 (8): e70317. doi:10.1371/journal.pone.0070317. PMC 3734023. PMID 23940560.{{cite journal}} : CS1 maint: article number as page number (link) - ↑ Preston, TM; Cooper, LG; King, CA (1990). "Amoeboid locomotion of Naegleria gruberi: the effects of cytochalasin B on cell-substratum interactions and motile behavior".

Food searching strategies of animals are key to their success in heterogeneous environments. The optimal search strategy may include specialized random walks such as Levy walks with heavy power-law tail distributions, or persistent walks with preferred movement in a similar direction. We have investigated the movement of the soil amoebae Dictyostelium searching for food. Dictyostelium cells move by extending pseudopodia, either in the direction of the previous pseudopod (persistent step) or in a different direction (turn). The analysis of ∼4000 pseudopodia reveals that step and turn pseudopodi

accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia ("false-feet") and posterior uropods. One or more pseudopodia may be Amoeboid movement is the most typical mode of locomotion in adherent eukaryotic cells. It is a crawling-like type of movement accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia ("false-feet") and posterior uropods. One or more pseudopodia may be produced at a time depending on the organism, but all amoeboid movement is characterized by the movement of organi Amoeboid movement is the most typical mode of locomotion in adherent eukaryotic cells. It is a crawling-like type of movement accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia ("false-feet") and posterior uropods. One or more pseudopodia may be produced at a time depending on the organism, but all amoeboid movement is characterized by the movement of organisms with an amorphous form that possess no set motility structures. Movement occurs when the cytoplasm slides and forms a pseudopodium in front to pull the cell forward. Some examples of organisms that exhibit this type of locomotion are amoebae (such as Amoeba proteus and Naegleria gruberi,) and slime molds, as well as some cells in humans such as leukocytes. Sarcomas, or cancers arising from connective tissue cells, are particularly adept at amoeboid movement, thus leading to their high rate of metastasis. This type of movement has been linked to changes in action potential. While several hypotheses have been proposed to explain the mechanism of amoeboid movement, its exact mechanisms are not…

Myosin IB null mutants of Dictyostelium exhibit abnormalities in motility. Cellular and intracellular motility are compared between normal Dictyostelium amoebae and amoebae lacking myosin IB (DMIB-). DMIB- cells generate elongated cell shapes, form particulate-free pseudopodia filled with F-actin, and exhibit an anterior bias in pseudopod extension in a fashion similar to normal amoebae. DMIB- cells also exhibit a normal response to the addition of the chemoattractant cAMP, including a depression in cellular and intracellular particle velocity, depolymerization of F-actin in pseudopodia, and a concomitant increase in cortical F-actin. DMIB- cells do, however, form lateral pseudopodia roughly three times as frequently as normal cells, turn more often, and exhibit depressed average instantaneous cell velocity. DMIB- cells also exhibit a decrease in the average instantaneous velocity of intracellular particle movement and an increase in the degree of randomness in particle direction.