Journal articles: 'Filopodium'

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Krndija, Denis, and Michael Fairhead. "IGF1R undergoes active and directed centripetal transport on filopodia upon receptor activation." Biochemical Journal 476, no. 23 (December 3, 2019): 3583–93. http://dx.doi.org/10.1042/bcj20190665.

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Filopodia are thin, actin-based membrane protrusions with roles in sensing external mechanical and chemical cues, such as growth factor gradients in tissues. It was proposed that the chemical sensing role of filopodia is achieved through clearance of activated signaling receptors from filopodia. Type I insulin-like growth factor receptor (IGF1R) is a key regulator of normal development and growth, as well as tumor development and progression. Its biological roles depend on its activation upon IGF1 binding at the cell membrane. IGF1R behavior at the cell membrane and in particular in filopodia, has not been established. We found that IGF1 activation led to a gradual reduction in IGF1R puncta in filopodia, and that this clearance depended on actin, non-muscle myosin II, and IGF1R kinase activity. Using single particle tracking of filopodial IGF1R, we established that ligand-free IGF1R undergoes non-directional unidimensional diffusion along the filopodium. Moreover, after initial diffusion, the ligand-bound IGF1R is actively transported along the filopodium towards the filopodium base, and consequently cleared from the filopodium. Our results show that IGF1R can move directionally on the plasma membrane protrusions, supporting a sensory role for filopodia in interpreting local IGF1 gradients.

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McConnell, Russell E., J. Edward van Veen, Marina Vidaki, Adam V. Kwiatkowski, Aaron S. Meyer, and Frank B. Gertler. "A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion." Journal of Cell Biology 213, no. 2 (April 18, 2016): 261–74. http://dx.doi.org/10.1083/jcb.201509062.

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Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.

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Marchenko, Olena O., Sulagna Das, Ji Yu, Igor L. Novak, Vladimir I. Rodionov, Nadia Efimova, Tatyana Svitkina, Charles W. Wolgemuth, and Leslie M. Loew. "A minimal actomyosin-based model predicts the dynamics of filopodia on neuronal dendrites." Molecular Biology of the Cell 28, no. 8 (April 15, 2017): 1021–33. http://dx.doi.org/10.1091/mbc.e16-06-0461.

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Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.

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Leijnse, Natascha, Lene B. Oddershede, and Poul M. Bendix. "Helical buckling of actin inside filopodia generates traction." Proceedings of the National Academy of Sciences 112, no. 1 (December 22, 2014): 136–41. http://dx.doi.org/10.1073/pnas.1411761112.

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Cells can interact with their surroundings via filopodia, which are membrane protrusions that extend beyond the cell body. Filopodia are essential during dynamic cellular processes like motility, invasion, and cell–cell communication. Filopodia contain cross-linked actin filaments, attached to the surrounding cell membrane via protein linkers such as integrins. These actin filaments are thought to play a pivotal role in force transduction, bending, and rotation. We investigated whether, and how, actin within filopodia is responsible for filopodia dynamics by conducting simultaneous force spectroscopy and confocal imaging of F-actin in membrane protrusions. The actin shaft was observed to periodically undergo helical coiling and rotational motion, which occurred simultaneously with retrograde movement of actin inside the filopodium. The cells were found to retract beads attached to the filopodial tip, and retraction was found to correlate with rotation and coiling of the actin shaft. These results suggest a previously unidentified mechanism by which a cell can use rotation of the filopodial actin shaft to induce coiling and hence axial shortening of the filopodial actin bundle.

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Kim, Min-Cheol, Yaron R. Silberberg, Rohan Abeyaratne, Roger D. Kamm, and H. Harry Asada. "Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration." Proceedings of the National Academy of Sciences 115, no. 3 (January 2, 2018): E390—E399. http://dx.doi.org/10.1073/pnas.1717230115.

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Filopodia have a key role in sensing both chemical and mechanical cues in surrounding extracellular matrix (ECM). However, quantitative understanding is still missing in the filopodial mechanosensing of local ECM stiffness, resulting from dynamic interactions between filopodia and the surrounding 3D ECM fibers. Here we present a method for characterizing the stiffness of ECM that is sensed by filopodia based on the theory of elasticity and discrete ECM fiber. We have applied this method to a filopodial mechanosensing model for predicting directed cell migration toward stiffer ECM. This model provides us with a distribution of force and displacement as well as their time rate of changes near the tip of a filopodium when it is bound to the surrounding ECM fibers. Aggregating these effects in each local region of 3D ECM, we express the local ECM stiffness sensed by the cell and explain polarity in the cellular durotaxis mechanism.

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Heidemann, S. R., P. Lamoureux, and R. E. Buxbaum. "Growth cone behavior and production of traction force." Journal of Cell Biology 111, no. 5 (November 1, 1990): 1949–57. http://dx.doi.org/10.1083/jcb.111.5.1949.

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The growth cone must push its substrate rearward via some traction force in order to propel itself forward. To determine which growth cone behaviors produce traction force, we observed chick sensory growth cones under conditions in which force production was accommodated by movement of obstacles in the environment, namely, neurites of other sensory neurons or glass fibers. The movements of these obstacles occurred via three, different, stereotyped growth cone behaviors: (a) filopodial contractions, (b) smooth rearward movement on the dorsal surface of the growth cone, and (c) interactions with ruffling lamellipodia. More than 70% of the obstacle movements were caused by filopodial contractions in which the obstacle attached at the extreme distal end of a filopodium and moved only as the filopodium changed its extension. Filopodial contractions were characterized by frequent changes of obstacle velocity and direction. Contraction of a single filopodium is estimated to exert 50-90 microdyn of force, which can account for the pull exerted by chick sensory growth cones. Importantly, all five cases of growth cones growing over the top of obstacle neurites (i.e., geometry that mimics the usual growth cone/substrate interaction), were of the filopodial contraction type. Some 25% of obstacle movements occurred by a smooth backward movement along the top surface of growth cones. Both the appearance and rate of movements were similar to that reported for retrograde flow of cortical actin near the dorsal growth cone surface. Although these retrograde flow movements also exerted enough force to account for growth cone pulling, we did not observe such movements on ventral growth cone surfaces. Occasionally obstacles were moved by interaction with ruffling lamellipodia. However, we obtained no evidence for attachment of the obstacles to ruffling lamellipodia or for directed obstacle movements by this mechanism. These data suggest that chick sensory growth cones move forward by contractile activity of filopodia, i.e., isometric contraction on a rigid substrate. Our data argue against retrograde flow of actin producing traction force.

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Lau, Pak-ming, Robert S. Zucker, and David Bentley. "Induction of Filopodia by Direct Local Elevation of Intracellular Calcium Ion Concentration." Journal of Cell Biology 145, no. 6 (June 14, 1999): 1265–76. http://dx.doi.org/10.1083/jcb.145.6.1265.

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In neuronal growth cones, cycles of filopodial protrusion and retraction are important in growth cone translocation and steering. Alteration in intracellular calcium ion concentration has been shown by several indirect methods to be critically involved in the regulation of filopodial activity. Here, we investigate whether direct elevation of [Ca2+]i, which is restricted in time and space and is isolated from earlier steps in intracellular signaling pathways, can initiate filopodial protrusion. We raised [Ca2+]i level transiently in small areas of nascent axons near growth cones in situ by localized photolysis of caged Ca2+ compounds. After photolysis, [Ca2+]i increased from ∼60 nM to ∼1 μM within the illuminated zone, and then returned to resting level in ∼10–15 s. New filopodia arose in this area within 1–5 min, and persisted for ∼15 min. Elevation of calcium concentration within a single filopodium induced new branch filopodia. In neurons coinjected with rhodamine-phalloidin, F-actin was observed in dynamic cortical patches along nascent axons; after photolysis, new filopodia often emerged from these patches. These results indicate that local transient [Ca2+]i elevation is sufficient to induce new filopodia from nascent axons or from existing filopodia.

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Saha, Tanumoy, Isabel Rathmann, Abhiyan Viplav, Sadhana Panzade, Isabell Begemann, Christiane Rasch, Jürgen Klingauf, Maja Matis, and Milos Galic. "Automated analysis of filopodial length and spatially resolved protein concentration via adaptive shape tracking." Molecular Biology of the Cell 27, no. 22 (November 7, 2016): 3616–26. http://dx.doi.org/10.1091/mbc.e16-06-0406.

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Filopodia are dynamic, actin-rich structures that transiently form on a variety of cell types. To understand the underlying control mechanisms requires precise monitoring of localization and concentration of individual regulatory and structural proteins as filopodia elongate and subsequently retract. Although several methods exist that analyze changes in filopodial shape, a software solution to reliably correlate growth dynamics with spatially resolved protein concentration along the filopodium independent of bending, lateral shift, or tilting is missing. Here we introduce a novel approach based on the convex-hull algorithm for parallel analysis of growth dynamics and relative spatiotemporal protein concentration along flexible filopodial protrusions. Detailed in silico tests using various geometries confirm that our technique accurately tracks growth dynamics and relative protein concentration along the filopodial length for a broad range of signal distributions. To validate our technique in living cells, we measure filopodial dynamics and quantify spatiotemporal localization of filopodia-associated proteins during the filopodial extension–retraction cycle in a variety of cell types in vitro and in vivo. Together these results show that the technique is suitable for simultaneous analysis of growth dynamics and spatiotemporal protein enrichment along filopodia. To allow readily application by other laboratories, we share source code and instructions for software handling.

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Miyashita, Motoaki, Hiroshi Ohnishi, Hideki Okazawa, Hiroyasu Tomonaga, Akiko Hayashi, Tetsuro-Takahiro Fujimoto, Nobuhiko Furuya, and Takashi Matozaki. "Promotion of Neurite and Filopodium Formation by CD47: Roles of Integrins, Rac, and Cdc42." Molecular Biology of the Cell 15, no. 8 (August 2004): 3950–63. http://dx.doi.org/10.1091/mbc.e04-01-0019.

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Axon extension during development is guided by many factors, but the signaling mechanisms responsible for its regulation remain largely unknown. We have now investigated the role of the transmembrane protein CD47 in this process in N1E-115 neuroblastoma cells. Forced expression of CD47 induced the formation of neurites and filopodia. Furthermore, an Fc fusion protein containing the extracellular region of the CD47 ligand SHPS-1 induced filopodium formation, and this effect was enhanced by CD47 overexpression. SHPS-1–Fc also promoted neurite and filopodium formation triggered by serum deprivation. Inhibition of Rac or Cdc42 preferentially blocked CD47-induced formation of neurites and filopodia, respectively. Overexpression of CD47 resulted in the activation of both Rac and Cdc42. The extracellular region of CD47 was sufficient for the induction of neurite formation by forced expression, but the entire structure of CD47 was required for enhancement of filopodium formation by SHPS-1–Fc. Neurite formation induced by CD47 was also inhibited by a mAb to the integrin β3 subunit. These results indicate that the interaction of SHPS-1 with CD47 promotes neurite and filopodium formation through the activation of Rac and Cdc42, and that integrins containing the β3 subunit participate in the effect of CD47 on neurite formation.

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10

Mallavarapu, Aneil, and Tim Mitchison. "Regulated Actin Cytoskeleton Assembly at Filopodium Tips Controls Their Extension and Retraction." Journal of Cell Biology 146, no. 5 (September 6, 1999): 1097–106. http://dx.doi.org/10.1083/jcb.146.5.1097.

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The extension and retraction of filopodia in response to extracellular cues is thought to be an important initial step that determines the direction of growth cone advance. We sought to understand how the dynamic behavior of the actin cytoskeleton is regulated to produce extension or retraction. By observing the movement of fiduciary marks on actin filaments in growth cones of a neuroblastoma cell line, we found that filopodium extension and retraction are governed by a balance between the rate of actin cytoskeleton assembly at the tip and retrograde flow. Both assembly and flow rate can vary with time in a single filopodium and between filopodia in a single growth cone. Regulation of assembly rate is the dominant factor in controlling filopodia behavior in our system.

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Xue, Fei, Deanna M. Janzen, and David A. Knecht. "Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction." International Journal of Cell Biology 2010 (2010): 1–13. http://dx.doi.org/10.1155/2010/507821.

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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 byα-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.

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Schäfer, Claudia, Uta Faust, Norbert Kirchgeßner, Rudolf Merkel, and Bernd Hoffmann. "The filopodium." Cell Adhesion & Migration 5, no. 5 (September 2011): 431–38. http://dx.doi.org/10.4161/cam.5.5.17400.

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Tamada, Atsushi, Satoshi Kawase, Fujio Murakami, and Hiroyuki Kamiguchi. "Autonomous right-screw rotation of growth cone filopodia drives neurite turning." Journal of Cell Biology 188, no. 3 (February 1, 2010): 429–41. http://dx.doi.org/10.1083/jcb.200906043.

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The direction of neurite elongation is controlled by various environmental cues. However, it has been reported that even in the absence of any extrinsic directional signals, neurites turn clockwise on two-dimensional substrates. In this study, we have discovered autonomous rotational motility of the growth cone, which provides a cellular basis for inherent neurite turning. We have developed a technique for monitoring three-dimensional motility of growth cone filopodia and demonstrate that an individual filopodium rotates on its own longitudinal axis in the right-screw direction from the viewpoint of the growth cone body. We also show that the filopodial rotation involves myosins Va and Vb and may be driven by their spiral interactions with filamentous actin. Furthermore, we provide evidence that the unidirectional rotation of filopodia causes deflected neurite elongation, most likely via asymmetric positioning of the filopodia onto the substrate. Although the growth cone itself has been regarded as functionally symmetric, our study reveals the asymmetric nature of growth cone motility.

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Passey, S., S. Pellegrin, and H. Mellor. "What is in a filopodium? Starfish versus hedgehogs." Biochemical Society Transactions 32, no. 6 (October 26, 2004): 1115–17. http://dx.doi.org/10.1042/bst0321115.

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Many cell types can generate thin actin-based protrusive structures, which are often classified under the general term of ‘filopodia’. However, a range of filopodia-like structures exists that differ both morphologically and functionally. In this brief review, we discuss the different types of filopodial structures, together with the actin-binding proteins and signalling pathways involved in their formation. Specifically, we highlight the differences between the filopodial extensions induced by the Rho GTPases Cdc42 and Rif.

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Svitkina, Tatyana M., Elena A. Bulanova, Oleg Y. Chaga, Danijela M. Vignjevic, Shin-ichiro Kojima, Jury M. Vasiliev, and Gary G. Borisy. "Mechanism of filopodia initiation by reorganization of a dendritic network." Journal of Cell Biology 160, no. 3 (February 3, 2003): 409–21. http://dx.doi.org/10.1083/jcb.200210174.

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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.

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Anderson, Tom W., Andrew N. Vaughan, and Louise P. Cramer. "Retrograde Flow and Myosin II Activity within the Leading Cell Edge Deliver F-Actin to the Lamella to Seed the Formation of Graded Polarity Actomyosin II Filament Bundles in Migrating Fibroblasts." Molecular Biology of the Cell 19, no. 11 (November 2008): 5006–18. http://dx.doi.org/10.1091/mbc.e08-01-0034.

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In migrating fibroblasts actomyosin II bundles are graded polarity (GP) bundles, a distinct organization to stress fibers. GP bundles are important for powering cell migration, yet have an unknown mechanism of formation. Electron microscopy and the fate of photobleached marks show actin filaments undergoing retrograde flow in filopodia, and the lamellipodium are structurally and dynamically linked with stationary GP bundles within the lamella. An individual filopodium initially protrudes, but then becomes separated from the tip of the lamellipodium and seeds the formation of a new GP bundle within the lamella. In individual live cells expressing both GFP-myosin II and RFP-actin, myosin II puncta localize to the base of an individual filopodium an average 28 s before the filopodium seeds the formation of a new GP bundle. Associated myosin II is stationary with respect to the substratum in new GP bundles. Inhibition of myosin II motor activity in live cells blocks appearance of new GP bundles in the lamella, without inhibition of cell protrusion in the same timescale. We conclude retrograde F-actin flow and myosin II activity within the leading cell edge delivers F-actin to the lamella to seed the formation of new GP bundles.

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Wu, D. Y., and D. J. Goldberg. "Regulated tyrosine phosphorylation at the tips of growth cone filopodia." Journal of Cell Biology 123, no. 3 (November 1, 1993): 653–64. http://dx.doi.org/10.1083/jcb.123.3.653.

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Several types of evidence suggest that protein-tyrosine phosphorylation is important during the growth of neuronal processes, but few specific roles, or subcellular localizations suggestive of such roles, have been defined. We report here a localization of tyrosine-phosphorylated protein at the tips of growth cone filopodia. Immunocytochemistry using a mAb to phosphorylated tyrosine residues revealed intense staining of the tips of most filopodia of Aplysia axons growing slowly on a polylysine substrate, but of few filopodia of axons growing rapidly on a substrate coated with Aplysia hemolymph, which has growth-promoting material. Cytochalasin D, which causes F-actin to withdraw rapidly from the growth cone, caused the tyrosine-phosphorylated protein to withdraw rapidly from filopodia, suggesting that the protein associates or interacts with actin filaments. Phosphotyrosine has previously been found concentrated at adherens junctions, where bundles of actin filaments terminate, but video-enhanced contrast-differential interference contrast and confocal interference reflection microscopy demonstrated that the filopodial tips were not adherent to the substrate. Acute application of either hemolymph or inhibitors of protein-tyrosine kinases to neurons on polylysine resulted in a rapid loss of intense staining at filopodial tips concomitant with a lengthening of the filopodia (and their core bundles of actin filaments). These results demonstrate that tyrosine-phosphorylated protein can be concentrated at the barbed ends of actin filaments in a context other than an adherens junction, indicate an association between changes in phosphorylation and filament dynamics, and provide evidence for tyrosine phosphorylation as a signaling mechanism in the filopodium that can respond to environmental cues controlling growth cone dynamics.

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Liberman, Asaf, Matan Mussel, Danny Kario, David Sprinzak, and Uri Nevo. "Modelling cell surface dynamics and cell–cell interactions using Cell Studio: a three-dimensional visualization tool based on gaming technology." Journal of The Royal Society Interface 16, no. 160 (November 2019): 20190264. http://dx.doi.org/10.1098/rsif.2019.0264.

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Predictive modelling of complex biological systems and biophysical interactions requires the inclusion of multiple nano- and micro-scale events. In many scenarios, however, numerical solutions alone do not necessarily enhance the understanding of the system. Instead, this work explores the use of an agent-based model with visualization capabilities to elucidate interactions between single cells. We present a model of juxtacrine signalling, using Cell Studio, an agent-based modelling system, based on gaming and three-dimensional visualization tools. The main advantages of the system are its ability to apply any cell geometry and to dynamically visualize the diffusion and interactions of the molecules within the cells in real time. These provide an excellent tool for obtaining insight about different biological scenarios, as the user may view the dynamics of a system and observe its emergent behaviour as it unfolds. The agent-based model was validated against the results of a mean-field model of Notch receptors and ligands in two neighbouring cells. The conversion to an agent-based model is described in detail. To demonstrate the advantages of the model, we further created a filopodium-mediated signalling model. Our model revealed that diffusion and endocytosis alone are insufficient to produce significant signalling in a filopodia scenario. This is due to the bottleneck at the cell–filopodium contact region and the long distance to the end of the filopodium. However, allowing active transport of ligands into filopodia enhances the signalling significantly compared with a face-to-face scenario. We conclude that the agent-based approach can provide insights into mechanisms underlying cell signalling. The open-source model can be found in the Internet hosting service GitHub.

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Robens, Jeffrey M., Lee Yeow-Fong, Elsa Ng, Christine Hall, and Ed Manser. "Regulation of IRSp53-Dependent Filopodial Dynamics by Antagonism between 14-3-3 Binding and SH3-Mediated Localization." Molecular and Cellular Biology 30, no. 3 (November 23, 2009): 829–44. http://dx.doi.org/10.1128/mcb.01574-08.

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ABSTRACT Filopodia are dynamic structures found at the leading edges of most migrating cells. IRSp53 plays a role in filopodium dynamics by coupling actin elongation with membrane protrusion. IRSp53 is a Cdc42 effector protein that contains an N-terminal inverse-BAR (Bin-amphipysin-Rvs) domain (IRSp53/MIM homology domain [IMD]) and an internal SH3 domain that associates with actin regulatory proteins, including Eps8. We demonstrate that the SH3 domain functions to localize IRSp53 to lamellipodia and that IRSp53 mutated in its SH3 domain fails to induce filopodia. Through SH3 domain-swapping experiments, we show that the related IRTKS SH3 domain is not functional in lamellipodial localization. IRSp53 binds to 14-3-3 after phosphorylation in a region that lies between the CRIB and SH3 domains. This association inhibits binding of the IRSp53 SH3 domain to proteins such as WAVE2 and Eps8 and also prevents Cdc42-GTP interaction. The antagonism is achieved by phosphorylation of two related 14-3-3 binding sites at T340 and T360. In the absence of phosphorylation at these sites, filopodium lifetimes in cells expressing exogenous IRSp53 are extended. Our work does not conform to current views that the inverse-BAR domain or Cdc42 controls IRSp53 localization but provides an alternative model of how IRSp53 is recruited (and released) to carry out its functions at lamellipodia and filopodia.

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SUETSUGU, Shiro, Tohru TEZUKA, Toshifumi MORIMURA, Mitsuharu HATTORI, Katsuhiko MIKOSHIBA, Tadashi YAMAMOTO, and Tadaomi TAKENAWA. "Regulation of actin cytoskeleton by mDab1 through N-WASP and ubiquitination of mDab1." Biochemical Journal 384, no. 1 (November 9, 2004): 1–8. http://dx.doi.org/10.1042/bj20041103.

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Migration of cells is critical to development of the central nervous system. Reelin, which was identified from the reeler mutant mice having a defect in the multilamellar structure of the brain, is thought to be a key signalling molecule that functions as a cue for determination of cell position. mDab1 (mouse Disabled homologue 1) functions downstream of Reelin. However, the mechanism by which mDab1 regulates cell migration during brain development is unknown. In the present paper, we show that mDab1 associates with N-WASP (neuronal Wiskott–Aldrich syndrome protein) in vitro and in brains of embryonic mice. mDab1 activates N-WASP directly, and induces actin polymerization through the Arp2/3 (actin-related protein 2/3) complex. mDab1 induces formation of filopodia when it is overexpressed in COS-7 cells. This filopodium formation is dependent on N-WASP, because expression of an N-WASP mutant that cannot induce Arp2/3-complex-mediated actin polymerization suppressed filopodium formation. The PTB (phosphotyrosine-binding) domain of mDab1 binds to N-WASP via the NRFY (Asn-Arg-Phe-Tyr) sequence close to the CRIB (Cdc42/Rac-interactive binding) motif of N-WASP and activates N-WASP in vitro. When mDab1 is phosphorylated by Fyn kinase in COS-7 cells, mDab1 is ubiquitinated in a Cbl-dependent manner, and mDab1 does not induce filopodium in the presence of activated Fyn. These findings suggest that mDab1 regulates the actin cytoskeleton through N-WASP, which is negatively regulated by phosphorylation-mediated ubiquitination of mDab1.

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Chiang, Tsai-Shin, Hsu-Feng Wu, and Fang-Jen S. Lee. "ADP-ribosylation factor–like 4C binding to filamin-A modulates filopodium formation and cell migration." Molecular Biology of the Cell 28, no. 22 (November 2017): 3013–28. http://dx.doi.org/10.1091/mbc.e17-01-0059.

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Changes in cell morphology and the physical forces that occur during migration are generated by a dynamic filamentous actin cytoskeleton. The ADP-ribosylation factor–like 4C (Arl4C) small GTPase acts as a molecular switch to regulate morphological changes and cell migration, although the mechanism by which this occurs remains unclear. Here we report that Arl4C functions with the actin regulator filamin-A (FLNa) to modulate filopodium formation and cell migration. We found that Arl4C interacted with FLNa in a GTP-dependent manner and that FLNa IgG repeat 22 is both required and sufficient for this interaction. We also show that interaction between FLNa and Arl4C is essential for Arl4C-induced filopodium formation and increases the association of FLNa with Cdc42-GEF FGD6, promoting cell division cycle 42 (Cdc42) GTPase activation. Thus our study revealed a novel mechanism, whereby filopodium formation and cell migration are regulated through the Arl4C-FLNa–mediated activation of Cdc42.

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Nguyen, Cuong Thach, Nhat-Tu Le, Thao Dang-Hien Tran, Eun-Hye Kim, Sang-Sang Park, Truc Thanh Luong, Kyung-Tae Chung, Suhkneung Pyo, and Dong-Kwon Rhee. "Streptococcus pneumoniae ClpL Modulates Adherence to A549 Human Lung Cells through Rap1/Rac1 Activation." Infection and Immunity 82, no. 9 (June 30, 2014): 3802–10. http://dx.doi.org/10.1128/iai.02012-14.

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ABSTRACTCaseinolytic protease L (ClpL) is a member of the HSP100/Clp chaperone family, which is found mainly in Gram-positive bacteria. ClpL is highly expressed during infection for refolding of stress-induced denatured proteins, some of which are important for adherence. However, the role of ClpL in modulating pneumococcal virulence is poorly understood. Here, we show that ClpL impairs pneumococcal adherence to A549 lung cells by inducing and activating Rap1 and Rac1, thus increasing phosphorylation of cofilin (inactive form). Moreover, infection with aclpLmutant (ΔclpL) causes a greater degree of filopodium formation than D39 wild-type (WT) infection. Inhibition of Rap1 and Rac1 impairs filopodium formation and pneumococcal adherence. Therefore, ClpL can reduce pneumococcal adherence to A549 cells, likely via modulation of Rap1- and Rac1-mediated filopodium formation. These results demonstrate a potential role for ClpL in pneumococcal resistance to host cell adherence during infection. This study provides insight into further understanding the interactions between hosts and pathogens.

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Ahmed, Sohail, Wah Ing Goh, and Wenyu Bu. "I-BAR domains, IRSp53 and filopodium formation." Seminars in Cell & Developmental Biology 21, no. 4 (June 2010): 350–56. http://dx.doi.org/10.1016/j.semcdb.2009.11.008.

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Goh, Wah Ing, Kim Buay Lim, Thankiah Sudhaharan, Kai Ping Sem, Wenyu Bu, Ai Mei Chou, and Sohail Ahmed. "mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation." Journal of Biological Chemistry 287, no. 7 (December 17, 2011): 4702–14. http://dx.doi.org/10.1074/jbc.m111.305102.

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Goldberg, DJ, and DW Burmeister. "Microtubule-based filopodium-like protrusions form after axotomy." Journal of Neuroscience 12, no. 12 (December 1, 1992): 4800–4807. http://dx.doi.org/10.1523/jneurosci.12-12-04800.1992.

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Daniels, D. R. "Effect of Capping Protein on a Growing Filopodium." Biophysical Journal 98, no. 7 (April 2010): 1139–48. http://dx.doi.org/10.1016/j.bpj.2009.11.053.

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Korobova, Farida, and Tatyana Svitkina. "Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis." Molecular Biology of the Cell 21, no. 1 (January 2010): 165–76. http://dx.doi.org/10.1091/mbc.e09-07-0596.

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Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as dendritic filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated filopodia-like protrusions. Dynamically, dendritic filopodia emerged from densities in the dendritic shaft, which by electron microscopy contained branched actin network associated with dendritic microtubules. We propose that dendritic spine morphogenesis begins from an actin patch elongating into a dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.

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Romero, S., A. Quatela, T. Bornschlogl, S. Guadagnini, P. Bassereau, and G. Tran Van Nhieu. "Filopodium retraction is controlled by adhesion to its tip." Journal of Cell Science 125, no. 21 (August 16, 2012): 4999–5004. http://dx.doi.org/10.1242/jcs.104778.

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Romero, Stephane, Alessia Quatela, Thomas Bornschlögl, Stéphanie Guadagnini, Patricia Bassereau, and Guy Tran Van Nhieu. "Filopodium retraction is controlled by adhesion to its tip." Journal of Cell Science 125, no. 22 (November 15, 2012): 5587. http://dx.doi.org/10.1242/jcs.126540.

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Heiman, Maxwell G., and Shai Shaham. "Twigs into branches: how a filopodium becomes a dendrite." Current Opinion in Neurobiology 20, no. 1 (February 2010): 86–91. http://dx.doi.org/10.1016/j.conb.2009.10.016.

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Xue, Niannan, Cristina Bertulli, Amine Sadok, and Yan Yan Shery Huang. "Dynamics of filopodium-like protrusion and endothelial cellular motility on one-dimensional extracellular matrix fibrils." Interface Focus 4, no. 2 (April 6, 2014): 20130060. http://dx.doi.org/10.1098/rsfs.2013.0060.

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Endothelial filopodia play key roles in guiding the tubular sprouting during angiogenesis. However, their dynamic morphological characteristics, with the associated implications in cell motility, have been subjected to limited investigations. In this work, the interaction between endothelial cells and extracellular matrix fibrils was recapitulated in vitro , where a specific focus was paid to derive the key morphological parameters to define the dynamics of filopodium-like protrusion during cell motility. Based on one-dimensional gelatin fibrils patterned by near-field electrospinning (NFES), we study the response of endothelial cells (EA.hy926) under normal culture or ROCK inhibition. It is shown that the behaviour of temporal protrusion length versus cell motility can be divided into distinct modes. Persistent migration was found to be one of the modes which permitted cell displacement for over 300 µm at a speed of approximately 1 µm min −1 . ROCK inhibition resulted in abnormally long protrusions and diminished the persistent migration, but dramatically increased the speeds of protrusion extension and retraction. Finally, we also report the breakage of protrusion during cell motility, and examine its phenotypic behaviours.

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Puchalapalli, Madhavi, Liang Mu, Chevaunne Edwards, Benjamin Kaplan-Singer, Pearl Eni, Kiran Belani, David Finkelstein, Arpan Patel, Megan Sayyad, and Jennifer E. Koblinski. "The Laminin-α1 Chain-Derived Peptide, AG73, Binds to Syndecans on MDA-231 Breast Cancer Cells and Alters Filopodium Formation." Analytical Cellular Pathology 2019 (April 30, 2019): 1–10. http://dx.doi.org/10.1155/2019/9192516.

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Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis.

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Czuchra, Aleksandra, Xunwei Wu, Hannelore Meyer, Jolanda van Hengel, Timm Schroeder, Robert Geffers, Klemens Rottner, and Cord Brakebusch. "Cdc42 Is Not Essential for Filopodium Formation, Directed Migration, Cell Polarization, and Mitosis in Fibroblastoid Cells." Molecular Biology of the Cell 16, no. 10 (October 2005): 4473–84. http://dx.doi.org/10.1091/mbc.e05-01-0061.

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Cdc42 is a small GTPase involved in the regulation of the cytoskeleton and cell polarity. To test whether Cdc42 has an essential role in the formation of filopodia or directed cell migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi apparatus into the direction of migration was decreased. However, expression of dominant negative Cdc42 in Cdc42-null cells resulted in strongly reduced directed migration, severely reduced single cell directionality, and complete loss of Golgi polarization and of directionality of protrusion formation toward the wound, as well as membrane blebbing. Thus, our data show that besides Cdc42 additional GTPases of the Rho-family, which share GEFs with Cdc42, are involved in the establishment and maintenance of cell polarity during directed migration.

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Martinez-Quiles, Narcisa, Rajat Rohatgi, Inés M. Antón, Miguel Medina, Stephen P. Saville, Hiroaki Miki, Hideki Yamaguchi, et al. "WIP regulates N-WASP-mediated actin polymerization and filopodium formation." Nature Cell Biology 3, no. 5 (April 11, 2001): 484–91. http://dx.doi.org/10.1038/35074551.

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Crespi, A., I. Ferrari, P. Lonati, A. Disanza, D. Fornasari, G. Scita, V. Padovano, and G. Pietrini. "LIN7 regulates the filopodium- and neurite-promoting activity of IRSp53." Journal of Cell Science 125, no. 19 (July 5, 2012): 4543–54. http://dx.doi.org/10.1242/jcs.106484.

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Chen, Kuan-Wei, Yu-Jung Chang, and Linyi Chen. "SH2B1 orchestrates signaling events to filopodium formation during neurite outgrowth." Communicative & Integrative Biology 8, no. 4 (July 4, 2015): e1044189. http://dx.doi.org/10.1080/19420889.2015.1044189.

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Hu, Hsiao-Tang, and Yi-Ping Hsueh. "Calcium influx and postsynaptic proteins coordinate the dendritic filopodium-spine transition." Developmental Neurobiology 74, no. 10 (April 28, 2014): 1011–29. http://dx.doi.org/10.1002/dneu.22181.

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Miao, Long, Kexi Yi, Joy M. Mackey, and Thomas M. Roberts. "Reconstitution in vitro of MSP-based filopodium extension in nematode sperm." Cell Motility and the Cytoskeleton 64, no. 4 (2007): 235–47. http://dx.doi.org/10.1002/cm.20177.

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Schirenbeck, A., R. Arasada, T. Bretschneider, T. E. B. Stradal, M. Schleicher, and J. Faix. "The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation." Proceedings of the National Academy of Sciences 103, no. 20 (May 4, 2006): 7694–99. http://dx.doi.org/10.1073/pnas.0511243103.

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Mashanov, Gregory I., Tatiana A. Nenasheva, Francine Parker, Laura Knipe, Michelle Peckham, and Justin E. Molloy. "Stepwise Movement of Myosin-10 Within the Filopodium of Live Mammalian Cells." Biophysical Journal 118, no. 3 (February 2020): 607a. http://dx.doi.org/10.1016/j.bpj.2019.11.3277.

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Nishimura, Tamako, Takuya Oyama, Hooi Ting Hu, Toshifumi Fujioka, Kyoko Hanawa-Suetsugu, Kazutaka Ikeda, Sohei Yamada, et al. "Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells." Developmental Cell 56, no. 6 (March 2021): 842–59. http://dx.doi.org/10.1016/j.devcel.2021.02.029.

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Nobile, Cinzia, Dominika Rudnicka, Milena Hasan, Nathalie Aulner, Françoise Porrot, Christophe Machu, Olivier Renaud, et al. "HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes." Journal of Virology 84, no. 5 (December 16, 2009): 2282–93. http://dx.doi.org/10.1128/jvi.02230-09.

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ABSTRACT The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV with nef deleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells.

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Oliver, Carey J., Ryan T. Terry-Lorenzo, Elizabeth Elliott, Wendy A. Christensen Bloomer, Shi Li, David L. Brautigan, Roger J. Colbran, and Shirish Shenolikar. "Targeting Protein Phosphatase 1 (PP1) to the Actin Cytoskeleton: the Neurabin I/PP1 Complex Regulates Cell Morphology." Molecular and Cellular Biology 22, no. 13 (July 1, 2002): 4690–701. http://dx.doi.org/10.1128/mcb.22.13.4690-4701.2002.

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ABSTRACT Neurabin I, a neuronal actin-binding protein, binds protein phosphatase 1 (PP1) and p70 ribosomal S6 protein kinase (p70S6K), both proteins implicated in cytoskeletal dynamics. We expressed wild-type and mutant neurabins fused to green fluorescent protein in Cos7, HEK293, and hippocampal neurons. Biochemical and cellular studies showed that an N-terminal F-actin-binding domain dictated neurabin I localization at actin cytoskeleton and promoted disassembly of stress fibers. Deletion of the C-terminal coiled-coil and sterile alpha motif domains abolished neurabin I dimerization and induced filopodium extension. Immune complex assays showed that neurabin I recruited an active PP1 via a PP1-docking sequence,457KIKF460. Mutation of the PP1-binding motif or PP1 inhibition by okadaic acid and calyculin A abolished filopodia and restored stress fibers in cells expressing neurabin I. In vitro and in vivo studies suggested that the actin-binding domain attenuated protein kinase A (PKA) phosphorylation of neurabin I. Modification of a major PKA site, serine-461, impaired PP1 binding. Finally, p70S6K was excluded from neurabin I/PP1 complexes and required the displacement of PP1 for recruitment to neurabin I. These studies provided new insights into the assembly and regulation of a neurabin I/PP1 complex that controls actin rearrangement to promote spine development in mammalian neurons.

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Shibue, Tsukasa, Mary W. Brooks, M. Fatih Inan, Ferenc Reinhardt, and Robert A. Weinberg. "The Outgrowth of Micrometastases Is Enabled by the Formation of Filopodium-like Protrusions." Cancer Discovery 2, no. 8 (May 18, 2012): 706–21. http://dx.doi.org/10.1158/2159-8290.cd-11-0239.

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Miki, Hiroaki, Takuya Sasaki, Yoshimi Takai, and Tadaomi Takenawa. "Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP." Nature 391, no. 6662 (January 1998): 93–96. http://dx.doi.org/10.1038/34208.

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Haviv, L., Y. Brill-Karniely, R. Mahaffy, F. Backouche, A. Ben-Shaul, T. D. Pollard, and A. Bernheim-Groswasser. "Reconstitution of the transition from lamellipodium to filopodium in a membrane-free system." Proceedings of the National Academy of Sciences 103, no. 13 (March 20, 2006): 4906–11. http://dx.doi.org/10.1073/pnas.0508269103.

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Knyazev, Nickolay A., Stanislav V. Shmakov, Sofya A. Pechkovskaya, Alexander S. Filatov, Alexander V. Stepakov, Vitali M. Boitsov, and Natalia A. Filatova. "Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast." International Journal of Molecular Sciences 22, no. 15 (July 31, 2021): 8264. http://dx.doi.org/10.3390/ijms22158264.

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Novel heterocyclic compounds containing 3-spiro[3-azabicyclo[3.1.0]hexane]oxindole framework (4a, 4b and 4c) have been studied as potential antitumor agents. The in silico ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed on 4a–c compounds with promising antiproliferative activity, previously synthetized and screened against human erythroleukemic cell line K562 tumor cell line. Cytotoxicity of 4a–c against murine fibroblast 3T3 and SV-40 transformed murine fibroblast 3T3-SV40 cell lines were evaluated. The 4a and 4c compounds were cytotoxic against 3T3-SV40 cells in comparison with those of 3T3. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Using confocal microscopy, we found that with 4a and 4c treatment of 3T3 cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 82–97% of cells. The number of 3T3-SV40 cells with stress fibers increased to 7–30% against 2% in control. We discovered that transformed 3T3-SV40 cells after treatment with compounds 4a and 4c significantly reduced the number of cells with filopodium-like membrane protrusions (from 86 % in control cells to 6–18% after treatment), which indirectly suggests a decrease in cell motility. We can conclude that the studied compounds 4a and 4c have a cytostatic effect, which can lead to a decrease in the number of filopodium-like membrane protrusions.

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Young, Lorna E., Ernest G. Heimsath, and Henry N. Higgs. "Cell type–dependent mechanisms for formin-mediated assembly of filopodia." Molecular Biology of the Cell 26, no. 25 (December 15, 2015): 4646–59. http://dx.doi.org/10.1091/mbc.e15-09-0626.

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Filopodia are finger-like protrusions from the plasma membrane and are of fundamental importance to cellular physiology, but the mechanisms governing their assembly are still in question. One model, called convergent elongation, proposes that filopodia arise from Arp2/3 complex–nucleated dendritic actin networks, with factors such as formins elongating these filaments into filopodia. We test this model using constitutively active constructs of two formins, FMNL3 and mDia2. Surprisingly, filopodial assembly requirements differ between suspension and adherent cells. In suspension cells, Arp2/3 complex is required for filopodial assembly through either formin. In contrast, a subset of filopodia remains after Arp2/3 complex inhibition in adherent cells. In adherent cells only, mDia1 and VASP also contribute to filopodial assembly, and filopodia are disproportionately associated with focal adhesions. We propose an extension of the existing models for filopodial assembly in which any cluster of actin filament barbed ends in proximity to the plasma membrane, either Arp2/3 complex dependent or independent, can initiate filopodial assembly by specific formins.

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Zhuravlev, Pavel I., and Garegin A. Papoian. "Protein fluxes along the filopodium as a framework for understanding the growth-retraction dynamics." Cell Adhesion & Migration 5, no. 5 (September 2011): 448–56. http://dx.doi.org/10.4161/cam.5.5.17868.

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Wang, Chun-Chieh, Yu-Chiu Kao, Pei-Yin Chi, Ching-Wen Huang, Jiunn-Yuan Lin, Chia-Fu Chou, Ji-Yen Cheng, and Chau-Hwang Lee. "Asymmetric cancer-cell filopodium growth induced by electric-fields in a microfluidic culture chip." Lab Chip 11, no. 4 (2011): 695–99. http://dx.doi.org/10.1039/c0lc00155d.

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Journal articles on the topic 'Filopodium'

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