TY - JOUR AB - Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling. AU - Ritzau Jost, Andreas AU - Delvendahl, Igor AU - Rings, Annika AU - Byczkowicz, Niklas AU - Harada, Harumi AU - Shigemoto, Ryuichi AU - Hirrlinger, Johannes AU - Eilers, Jens AU - Hallermann, Stefan ID - 1898 IS - 1 JF - Neuron TI - Ultrafast action potentials mediate kilohertz signaling at a central synapse VL - 84 ER - TY - JOUR AB - In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets. AU - Arikan, Murat AU - Preiner, Reinhold AU - Scheiblauer, Claus AU - Jeschke, Stefan AU - Wimmer, Michael ID - 1906 IS - 9 JF - IEEE Transactions on Visualization and Computer Graphics TI - Large-scale point-cloud visualization through localized textured surface reconstruction VL - 20 ER - TY - JOUR AB - The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans-species evolution). AU - Tobler, Michael AU - Plath, Martin AU - Riesch, Rüdiger AU - Schlupp, Ingo AU - Grasse, Anna V AU - Munimanda, Gopi AU - Setzer, C AU - Penn, Dustin AU - Moodley, Yoshan ID - 1905 IS - 5 JF - Journal of Evolutionary Biology SN - 1010-061X TI - Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations VL - 27 ER - TY - JOUR AB - In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates. AU - Hall, Barry AU - Acar, Hande AU - Nandipati, Anna AU - Barlow, Miriam ID - 1902 IS - 1 JF - Molecular Biology and Evolution SN - 0737-4038 TI - Growth rates made easy VL - 31 ER - TY - JOUR AB - In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum that emerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxin response machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell maintenance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thus provides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is balanced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biology, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediated auxin production to IAA17-dependent repression of auxin responses. This WOX5-IAA17 feedback circuit further assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-IAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSC differentiation. AU - Tian, Huiyu AU - Wabnik, Krzysztof T AU - Niu, Tiantian AU - Li, Hongjiang AU - Yu, Qianqian AU - Pollmann, Stephan AU - Vanneste, Steffen AU - Govaerts, Willy AU - Rolčík, Jakub AU - Geisler, Markus AU - Friml, Jirí AU - Ding, Zhaojun ID - 1901 IS - 2 JF - Molecular Plant TI - WOX5-IAA17 feedback circuit-mediated cellular auxin response is crucial for the patterning of root stem cell niches in arabidopsis VL - 7 ER - TY - JOUR AB - We prove a Strichartz inequality for a system of orthonormal functions, with an optimal behavior of the constant in the limit of a large number of functions. The estimate generalizes the usual Strichartz inequality, in the same fashion as the Lieb-Thirring inequality generalizes the Sobolev inequality. As an application, we consider the Schrödinger equation with a time-dependent potential and we show the existence of the wave operator in Schatten spaces. AU - Frank, Rupert AU - Lewin, Mathieu AU - Lieb, Élliott AU - Seiringer, Robert ID - 1904 IS - 7 JF - Journal of the European Mathematical Society TI - Strichartz inequality for orthonormal functions VL - 16 ER - TY - JOUR AB - Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions. AU - Behrndt, Martin AU - Heisenberg, Carl-Philipp J ID - 1900 IS - 2 JF - Nature Cell Biology TI - Lateral junction dynamics lead the way out VL - 16 ER - TY - JOUR AB - Summary: Phenotypes are often environmentally dependent, which requires organisms to track environmental change. The challenge for organisms is to construct phenotypes using the most accurate environmental cue. Here, we use a quantitative genetic model of adaptation by additive genetic variance, within- and transgenerational plasticity via linear reaction norms and indirect genetic effects respectively. We show how the relative influence on the eventual phenotype of these components depends on the predictability of environmental change (fast or slow, sinusoidal or stochastic) and the developmental lag τ between when the environment is perceived and when selection acts. We then decompose expected mean fitness into three components (variance load, adaptation and fluctuation load) to study the fitness costs of within- and transgenerational plasticity. A strongly negative maternal effect coefficient m minimizes the variance load, but a strongly positive m minimises the fluctuation load. The adaptation term is maximized closer to zero, with positive or negative m preferred under different environmental scenarios. Phenotypic plasticity is higher when τ is shorter and when the environment changes frequently between seasonal extremes. Expected mean population fitness is highest away from highest observed levels of phenotypic plasticity. Within- and transgenerational plasticity act in concert to deliver well-adapted phenotypes, which emphasizes the need to study both simultaneously when investigating phenotypic evolution. AU - Ezard, Thomas AU - Prizak, Roshan AU - Hoyle, Rebecca ID - 1909 IS - 3 JF - Functional Ecology TI - The fitness costs of adaptation via phenotypic plasticity and maternal effects VL - 28 ER - TY - JOUR AB - angerhans cells (LCs) are a unique subset of dendritic cells (DCs) that express epithelial adhesion molecules, allowing them to form contacts with epithelial cells and reside in epidermal/epithelial tissues. The dynamic regulation of epithelial adhesion plays a decisive role in the life cycle of LCs. It controls whether LCs remain immature and sessile within the epidermis or mature and egress to initiate immune responses. So far, the molecular machinery regulating epithelial adhesion molecules during LC maturation remains elusive. Here, we generated pure populations of immature human LCs in vitro to systematically probe for gene-expression changes during LC maturation. LCs down-regulate a set of epithelial genes including E-cadherin, while they upregulate the mesenchymal marker N-cadherin known to facilitate cell migration. In addition, N-cadherin is constitutively expressed by monocyte-derived DCs known to exhibit characteristics of both inflammatory-type and interstitial/dermal DCs. Moreover, the transcription factors ZEB1 and ZEB2 (ZEB is zinc-finger E-box-binding homeobox) are upregulated in migratory LCs. ZEB1 and ZEB2 have been shown to induce epithelial-to-mesenchymal transition (EMT) and invasive behavior in cancer cells undergoing metastasis. Our results provide the first hint that the molecular EMT machinery might facilitate LC mobilization. Moreover, our study suggests that N-cadherin plays a role during DC migration. AU - Konradi, Sabine AU - Yasmin, Nighat AU - Haslwanter, Denise AU - Weber, Michele AU - Gesslbauer, Bernd AU - Sixt, Michael K AU - Strobl, Herbert ID - 1910 IS - 2 JF - European Journal of Immunology TI - Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2 VL - 44 ER - TY - CONF AB - Most cryptographic security proofs require showing that two systems are indistinguishable. A central tool in such proofs is that of a game, where winning the game means provoking a certain condition, and it is shown that the two systems considered cannot be distinguished unless this condition is provoked. Upper bounding the probability of winning such a game, i.e., provoking this condition, for an arbitrary strategy is usually hard, except in the special case where the best strategy for winning such a game is known to be non-adaptive. A sufficient criterion for ensuring the optimality of non-adaptive strategies is that of conditional equivalence to a system, a notion introduced in [1]. In this paper, we show that this criterion is not necessary to ensure the optimality of non-adaptive strategies by giving two results of independent interest: 1) the optimality of non-adaptive strategies is not preserved under parallel composition; 2) in contrast, conditional equivalence is preserved under parallel composition. AU - Demay, Grégory AU - Gazi, Peter AU - Maurer, Ueli AU - Tackmann, Björn ID - 1907 T2 - IEEE International Symposium on Information Theory TI - Optimality of non-adaptive strategies: The case of parallel games ER - TY - JOUR AB - In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can bring together beneficial alleles from different backgrounds, but tightly linked alleles may still greatly interfere with each other. We show for well-mixed populations that when this interference is strong, the genome can be seen as consisting of many effectively asexual stretches linked together. The rate at which beneficial alleles fix is thus roughly proportional to the rate of recombination and depends only logarithmically on the mutation supply and the strength of selection. Our scaling arguments also allow us to predict, with reasonable accuracy, the fitness distribution of fixed mutations when the mutational effect sizes are broad. We focus on the regime in which crossovers occur more frequently than beneficial mutations, as is likely to be the case for many natural populations. AU - Weissman, Daniel AU - Hallatschek, Oskar ID - 1908 IS - 4 JF - Genetics TI - The rate of adaptation in large sexual populations with linear chromosomes VL - 196 ER - TY - JOUR AB - The topological Tverberg theorem has been generalized in several directions by setting extra restrictions on the Tverberg partitions. Restricted Tverberg partitions, defined by the idea that certain points cannot be in the same part, are encoded with graphs. When two points are adjacent in the graph, they are not in the same part. If the restrictions are too harsh, then the topological Tverberg theorem fails. The colored Tverberg theorem corresponds to graphs constructed as disjoint unions of small complete graphs. Hell studied the case of paths and cycles. In graph theory these partitions are usually viewed as graph colorings. As explored by Aharoni, Haxell, Meshulam and others there are fundamental connections between several notions of graph colorings and topological combinatorics. For ordinary graph colorings it is enough to require that the number of colors q satisfy q>Δ, where Δ is the maximal degree of the graph. It was proven by the first author using equivariant topology that if q>Δ 2 then the topological Tverberg theorem still works. It is conjectured that q>KΔ is also enough for some constant K, and in this paper we prove a fixed-parameter version of that conjecture. The required topological connectivity results are proven with shellability, which also strengthens some previous partial results where the topological connectivity was proven with the nerve lemma. AU - Engström, Alexander AU - Noren, Patrik ID - 1911 IS - 1 JF - Discrete & Computational Geometry TI - Tverberg's Theorem and Graph Coloring VL - 51 ER - TY - JOUR AB - Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease. AU - Novarino, Gaia AU - Fenstermaker, Ali AU - Zaki, Maha AU - Hofree, Matan AU - Silhavy, Jennifer AU - Heiberg, Andrew AU - Abdellateef, Mostafa AU - Rosti, Başak AU - Scott, Eric AU - Mansour, Lobna AU - Masri, Amira AU - Kayserili, Hülya AU - Al Aama, Jumana AU - Abdel Salam, Ghada AU - Karminejad, Ariana AU - Kara, Majdi AU - Kara, Bülent AU - Bozorgmehri, Bita AU - Ben Omran, Tawfeg AU - Mojahedi, Faezeh AU - Mahmoud, Iman AU - Bouslam, Naïma AU - Bouhouche, Ahmed AU - Benomar, Ali AU - Hanein, Sylvain AU - Raymond, Laure AU - Forlani, Sylvie AU - Mascaro, Massimo AU - Selim, Laila AU - Shehata, Nabil AU - Al Allawi, Nasir AU - Bindu, Parayil AU - Azam, Matloob AU - Günel, Murat AU - Caglayan, Ahmet AU - Bilgüvar, Kaya AU - Tolun, Aslihan AU - Issa, Mahmoud AU - Schroth, Jana AU - Spencer, Emily AU - Rosti, Rasim AU - Akizu, Naiara AU - Vaux, Keith AU - Johansen, Anide AU - Koh, Alice AU - Megahed, Hisham AU - Dürr, Alexandra AU - Brice, Alexis AU - Stévanin, Giovanni AU - Gabriel, Stacy AU - Ideker, Trey AU - Gleeson, Joseph ID - 1916 IS - 6170 JF - Science TI - Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders VL - 343 ER - TY - JOUR AB - Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown to be essential for plant development and morphogenesis, but its mode of action remains unclear. Here, we report that the plasma membrane-localized transmembrane kinase (TMK) receptor-like kinases interact with ABP1 and transduce auxin signal to activate plasma membrane-associated ROPs [Rho-like guanosine triphosphatases (GTPase) from plants], leading to changes in the cytoskeleton and the shape of leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the cell surface is induced by auxin and requires ABP1 sensing of auxin. These findings show that TMK proteins and ABP1 form a cell surface auxin perception complex that activates ROP signaling pathways, regulating nontranscriptional cytoplasmic responses and associated fundamental processes. AU - Xu, Tongda AU - Dai, Ning AU - Chen, Jisheng AU - Nagawa, Shingo AU - Cao, Min AU - Li, Hongjiang AU - Zhou, Zimin AU - Chen, Xu AU - De Rycke, Riet AU - Rakusová, Hana AU - Wang, Wen AU - Jones, Alan AU - Friml, Jirí AU - Patterson, Sara AU - Bleecker, Anthony AU - Yang, Zhenbiao ID - 1917 IS - 6174 JF - Science TI - Cell surface ABP1-TMK auxin sensing complex activates ROP GTPase signaling VL - 343 ER - TY - JOUR AB - Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-termadaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation. AU - Wang, Wen AU - Nakadate, Kazuhiko AU - Masugi Tokita, Miwako AU - Shutoh, Fumihiro AU - Aziz, Wajeeha AU - Tarusawa, Etsuko AU - Lörincz, Andrea AU - Molnár, Elek AU - Kesaf, Sebnem AU - Li, Yunqing AU - Fukazawa, Yugo AU - Nagao, Soichi AU - Shigemoto, Ryuichi ID - 1920 IS - 1 JF - PNAS TI - Distinct cerebellar engrams in short-term and long-term motor learning VL - 111 ER - TY - JOUR AB - ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small GTPases that function as essential molecular switches to control diverse cellular processes including cytoskeleton organization, cell polarization, cytokinesis, cell differentiation and vesicle trafficking. Although the machineries of vesicle trafficking and cell polarity in plants have been individually well addressed, how ROPs co-ordinate those processes is still largely unclear. Recent progress has been made towards an understanding of the coordination of ROP signalling and trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both root and leaf pavement cells. PIN transporters constantly shuttle between the endosomal compartments and the polar plasma membrane domains, therefore the modulation of PIN-dependent auxin transport between cells is a main developmental output of ROP-regulated vesicle trafficking. The present review focuses on these cellular mechanisms, especially the integration of ROP-based vesicle trafficking and plant cell polarity. AU - Chen, Xu AU - Friml, Jirí ID - 1915 IS - 1 JF - Biochemical Society Transactions SN - 0300-5127 TI - Rho-GTPase-regulated vesicle trafficking in plant cell polarity VL - 42 ER - TY - JOUR AB - Long-lasting memories are formed when the stimulus is temporally distributed (spacing effect). However, the synaptic mechanisms underlying this robust phenomenon and the precise time course of the synaptic modifications that occur during learning remain unclear. Here we examined the adaptation of horizontal optokinetic response in mice that underwent 1 h of massed and spaced training at varying intervals. Despite similar acquisition by all training protocols, 1 h of spacing produced the highest memory retention at 24 h, which lasted for 1 mo. The distinct kinetics of memory are strongly correlated with the reduction of floccular parallel fiber-Purkinje cell synapses but not with AMPA receptor (AMPAR) number and synapse size. After the spaced training, we observed 25%, 23%, and 12% reduction in AMPAR density, synapse size, and synapse number, respectively. Four hours after the spaced training, half of the synapses and Purkinje cell spines had been eliminated, whereas AMPAR density and synapse size were recovered in remaining synapses. Surprisingly, massed training also produced long-term memory and halving of synapses; however, this occurred slowly over days, and the memory lasted for only 1 wk. This distinct kinetics of structural plasticity may serve as a basis for unique temporal profiles in the formation and decay of memory with or without intervals. AU - Aziz, Wajeeha AU - Wang, Wen AU - Kesaf, Sebnem AU - Mohamed, Alsayed AU - Fukazawa, Yugo AU - Shigemoto, Ryuichi ID - 1919 IS - 1 JF - PNAS TI - Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning VL - 111 ER - TY - JOUR AB - As the nuclear charge Z is continuously decreased an N-electron atom undergoes a binding-unbinding transition. We investigate whether the electrons remain bound and whether the radius of the system stays finite as the critical value Zc is approached. Existence of a ground state at Zc is shown under the condition Zc < N-K, where K is the maximal number of electrons that can be removed at Zc without changing the energy. AU - Bellazzini, Jacopo AU - Frank, Rupert AU - Lieb, Élliott AU - Seiringer, Robert ID - 1918 IS - 1 JF - Reviews in Mathematical Physics TI - Existence of ground states for negative ions at the binding threshold VL - 26 ER - TY - JOUR AB - Targeting membrane proteins for degradation requires the sequential action of ESCRT sub-complexes ESCRT-0 to ESCRT-III. Although this machinery is generally conserved among kingdoms, plants lack the essential ESCRT-0 components. A new report closes this gap by identifying a novel protein family that substitutes for ESCRT-0 function in plants. AU - Sauer, Michael AU - Friml, Jirí ID - 1914 IS - 1 JF - Current Biology TI - Plant biology: Gatekeepers of the road to protein perdition VL - 24 ER - TY - JOUR AB - In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity. AU - Lamprecht, Constanze AU - Plochberger, Birgit AU - Ruprecht, Verena AU - Wieser, Stefan AU - Rankl, Christian AU - Heister, Elena AU - Unterauer, Barbara AU - Brameshuber, Mario AU - Danzberger, Jürgen AU - Lukanov, Petar AU - Flahaut, Emmanuel AU - Schütz, Gerhard AU - Hinterdorfer, Peter AU - Ebner, Andreas ID - 1925 IS - 12 JF - Nanotechnology TI - A single-molecule approach to explore binding uptake and transport of cancer cell targeting nanotubes VL - 25 ER -