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| Open AccessA functional family of fluorescent nucleotide analogues to investigate actin dynamics and energetics
Actin polymerization provides force for vital processes of the eukaryotic cell, but our understanding of actin dynamics and energetics remains limited due to the lack of high-quality probes. Here authors identify a family of highly sensitive fluorescent nucleotide analogues which bind to actin and provide energy to power actin-based processes.
- Jessica Colombo
- , Adrien Antkowiak
- & Alphée Michelot
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Article
| Open AccessAdhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion
Cell extrusion regulates monolayer cell density and is critical in maintaining epithelia integrity, which has implications in homeostasis, development, and cancer progression. Here the authors describe how monolayer integrate mechanical signals from tissue mechanics, cell-cell adhesion, cell-substrate adhesion and cytoskeleton coordinate cell extrusion.
- Anh Phuong Le
- , Jean-François Rupprecht
- & Benoît Ladoux
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| Open AccessA tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner
Activating adaptors that link dynein to its general cofactor dynactin recruit specific cargoes and regulate dynein’s activity and processive motility in retrograde transport. Here, the authors present the crystal structures of two adaptor complexes with the dynein light intermediate chain-1 (LIC1) and show that activating adaptors can be grouped into three structural classes based on their different interactions with LIC1.
- In-Gyun Lee
- , Sydney E. Cason
- & Roberto Dominguez
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Article
| Open AccessRegionalized tissue fluidization is required for epithelial gap closure during insect gastrulation
The mechanics of embryonic tissue spreading over spherical eggs is not fully understood. Here, the authors show that during gastrulation in the red flour beetle, extraembryonic tissue epiboly is facilitated by local actomyosin-mediated fluidization of the tissue at the leading edge.
- Akanksha Jain
- , Vladimir Ulman
- & Anastasios Pavlopoulos
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Article
| Open AccessCryopreservation impairs 3-D migration and cytotoxicity of natural killer cells
Cryopreservation is standard protocol prior to using NK cells in immunotherapy. Here the authors show that cryopreservation substantially reduces the clinical utility of these cells owing to a defect in their motility, an effect that might account for failure to treat some cancers with NK cell immunotherapy.
- Christoph Mark
- , Tina Czerwinski
- & Caroline J. Voskens
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Article
| Open AccessIn primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition
During repair, development, or cancer metastasis, epithelial cells can become migratory through partial or full epithelial to mesenchymal transition (EMT). Here, the authors report that differentiated epithelial collectives may undergo cooperative and collective migration without evidence of partial EMT through an unjamming transition (UJT).
- Jennifer A. Mitchel
- , Amit Das
- & Jin-Ah Park
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Article
| Open AccessOrthophosphate increases the efficiency of slow muscle-myosin isoform in the presence of omecamtiv mecarbil
Omecamtiv mecarbil is a small molecule effector under clinical trial for the treatment of systolic heart failure. Here the authors define the molecular mechanisms of its inotropic action and find it can increase the efficiency of contraction in muscle fibres when the orthophosphate concentration rises with the beat frequency.
- Serena Governali
- , Marco Caremani
- & Marco Linari
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Article
| Open AccessTug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement
Symmetric or asymmetric positioning of intracellular structures such as the nucleus and mitotic spindle steers various biological processes. Here authors use an in vitro model and show that a tug-of-war between centripetal actomyosin waves and percolation of bulk actomyosin network direct the positioning.
- Ryota Sakamoto
- , Masatoshi Tanabe
- & Makito Miyazaki
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Article
| Open AccessKinesin-14 motors drive a right-handed helical motion of antiparallel microtubules around each other
Some kinesins exhibit off-axis power strokes but their impact on motility and force generation in microtubule overlaps has not been investigated so far. Here authors use a 3D in vitro motility assay and find that Ndc’s off-axis motor forces generate torque in antiparallel microtubules which causes microtubule twisting and coiling.
- Aniruddha Mitra
- , Laura Meißner
- & Stefan Diez
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Article
| Open AccessDense active matter model of motion patterns in confluent cell monolayers
Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes. Here the authors show that cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce characteristic swirl-like correlations.
- Silke Henkes
- , Kaja Kostanjevec
- & Eric Bertin
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Article
| Open AccessStructural basis for two-way communication between dynein and microtubules
The movement of cytoplasmic dynein on microtubule tracks is coordinated by the microtubule-binding domain (MTBD) and the ATPase domain via a coiled-coil stalk. Here authors use NMR and cryo-EM and suggest that the communication between the ATPase-domain and MTBD is achieved by sliding of the stalk α-helix by a half-turn or one-turn.
- Noritaka Nishida
- , Yuta Komori
- & Masahide Kikkawa
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Article
| Open AccessHighly durable crack sensor integrated with silicone rubber cantilever for measuring cardiac contractility
Measuring cardiac contractility is challenging. Here, the authors encapsulated a crack-based sensor with polydimethylsiloxane, thereby endowing the sensor with the stability to measure cardiac contractility for up to 26 days as well as monitoring drug-induced cardiac toxicity in cell culture.
- Dong-Su Kim
- , Yong Whan Choi
- & Dong-Weon Lee
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Article
| Open AccessChemotactic behaviour of Escherichia coli at high cell density
Swimming bacteria perform collective motion at high cell density, yet it is unclear how this behaviour affects their ability to follow substance gradients in the environment. Here, Colin et al. address this question by studying motion of Escherichia coli in controlled chemical gradients.
- Remy Colin
- , Knut Drescher
- & Victor Sourjik
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Article
| Open AccessMyosin 1b is an actin depolymerase
Former evidence suggests a correlation between the function of non-conventional myosin motors and actin dynamics. Here authors use in vitro assays in which they observe that actin sliding on myosin 1b immobilized or bound to a fluid bilayer enhances actin depolymerization at the barbed end.
- Julien Pernier
- , Remy Kusters
- & Evelyne Coudrier
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Article
| Open AccessMolecular features of the UNC-45 chaperone critical for binding and folding muscle myosin
Myosin, a motor protein essential for intracellular transport to muscle contraction, requires a chaperone UNC-45 for folding and assembly. Here authors use in vitro reconstitution and structural biology to characterize the interplay between UNC-45 and muscle myosin MHC-B.
- Doris Hellerschmied
- , Anita Lehner
- & Tim Clausen
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Article
| Open AccessEnhanced propagation of motile bacteria on surfaces due to forward scattering
Microorganisms tend to live in heterogeneous environments. Here the authors investigate the influence of this heterogeneity on bacteria swimming near a surface in the presence of obstacles; these are found to enhance the cells’ propagation rather than hinder it for an optimal obstacle density.
- Stanislaw Makarchuk
- , Vasco C. Braz
- & Giorgio Volpe
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Article
| Open AccessPlasmodium myosin A drives parasite invasion by an atypical force generating mechanism
Here, Robert-Paganin et al. show that myosin A from Plasmodium falciparum is critical for red blood cell invasion and that non-canonical interactions and regulated phosphorylation are important for force generation during parasite invasion.
- Julien Robert-Paganin
- , James P. Robblee
- & Anne Houdusse
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Article
| Open AccessLive cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.
- Karl E. Bauer
- , Inmaculada Segura
- & Michael A. Kiebler
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| Open Accessβ-Cardiac myosin hypertrophic cardiomyopathy mutations release sequestered heads and increase enzymatic activity
Hypertrophic cardiomyopathy (HCM) leads to hyper-contractility of the heart and is often caused by mutations in human β-cardiac myosin. Here authors show that four separate β-cardiac myosin mutations can modulate myosin activity by disrupting intramolecular interactions.
- Arjun S. Adhikari
- , Darshan V. Trivedi
- & Kathleen M. Ruppel
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Article
| Open AccessInvariance properties of bacterial random walks in complex structures
It has been previously shown theoretically that the average path length of random walks inside a closed domain is invariant. Here the authors demonstrate that this invariance property can be used to predict the mean residence time of swimming bacteria exploring structured micro-environments.
- Giacomo Frangipane
- , Gaszton Vizsnyiczai
- & Roberto Di Leonardo
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| Open AccessBacterial hopping and trapping in porous media
Many bacteria swim with run-and-tumble motion in unconfined fluid. Here the authors report that confinement of these bacteria in a 3D porous medium changes this motion into hopping and trapping, in which the cells are intermittently and transiently trapped as they navigate the pore space.
- Tapomoy Bhattacharjee
- & Sujit S. Datta
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Article
| Open AccessDynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix
Macrophages play an important role in wound healing but the guidance cues driving macrophages to sites of repair are still not clear. Here the authors discover that macrophages are attracted to contracting fibroblasts by responding to locally sensed displacements of collagen fibres.
- Pardis Pakshir
- , Moien Alizadehgiashi
- & Boris Hinz
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Article
| Open AccessMicrotubule end conversion mediated by motors and diffusing proteins with no intrinsic microtubule end-binding activity
During cell division, it is currently unclear how kinetochores transit from lateral microtubule attachment to durable association to dynamic microtubule plus ends. Here, using in vitro reconstitution and computer modeling, the authors provide biophysical mechanism for microtubule end-conversion driven by two kinetochore components, CENP-E and Ndc80 complex
- Manas Chakraborty
- , Ekaterina V. Tarasovetc
- & Ekaterina L. Grishchuk
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Article
| Open AccessMultimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm
Methods to track molecular motion in eukaryotic cells mostly rely on fluorescent labels, transfection or photobleaching. Here the authors use multimodal partial wave spectroscopy to perform label-free live cell measurements of nanoscale structure and macromolecular motion with millisecond temporal resolution.
- Scott Gladstein
- , Luay M. Almassalha
- & Vadim Backman
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Article
| Open AccessRegulation of in vivo dynein force production by CDK5 and 14-3-3ε and KIAA0528
Dynein plays roles in vesicular, organelle, chromosomal and nuclear transport but so far it is unclear how dynein activity in cells is regulated. Here authors study several dynein cofactors and their role in force adaptation of dynein during lipid droplet, lysosomal, and mitochondrial transport.
- Dail E. Chapman
- , Babu J. N. Reddy
- & Steven P. Gross
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Article
| Open AccessBimodal sensing of guidance cues in mechanically distinct microenvironments
Invasive cells respond to contact guidance cues during migration. Here, using micro- and nanopatterning with different ligands and varying stiffness, the authors find that cells can make cellular protrusions through both contractility-dependent and contractility-independent means.
- Erdem D. Tabdanov
- , Vikram V. Puram
- & Paolo P. Provenzano
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Article
| Open AccessOptogenetic dissection of Rac1 and Cdc42 gradient shaping
A steep gradient of Cdc42 is at the front of migrating cells, whereas the active Rac1 gradient is graded. Here the authors show that Cdc42 gradients follow the distribution of GEFs and govern direction of migration, while Rac1 gradients require the activity of the GAP β2-chimaerin and control cell speed.
- S. de Beco
- , K. Vaidžiulytė
- & M. Coppey
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Article
| Open AccessVibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus
Prey bacteria have evolved different strategies to counteract predation but the genetic basis remains unclear. Here, Duncan et al. identify key genes involved in Vibrio cholerae sensitivity to Bdellovibrio bacteriovorus predation, providing new insights into prey resistance mechanisms.
- Miles C. Duncan
- , John C. Forbes
- & Andrew Camilli
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Article
| Open AccessLévy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo
- Sabil Huda
- , Bettina Weigelin
- & Bartosz A. Grzybowski
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Article
| Open AccessEngineering bacterial vortex lattice via direct laser lithography
Geometrically confined suspensions of swimming bacteria can self-organize into an ordered state. Here, the authors use tiny pillars to trigger organization of bacterial motion into a stable lattice of vortices with a long-range antiferromagnetic order and control vortex direction through pillar chirality.
- Daiki Nishiguchi
- , Igor S Aranson
- & Andrey Sokolov
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Article
| Open AccessMechanical interactions among followers determine the emergence of leaders in migrating epithelial cell collectives
During collective cell migration, how leader cells emerge is poorly understood. Here, the authors find that small groups of mechanically-interacting follower cells pull on the future leaders to stochastically elect them to their fate.
- Medhavi Vishwakarma
- , Jacopo Di Russo
- & Joachim P. Spatz
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Article
| Open AccessDissecting myosin-5B mechanosensitivity and calcium regulation at the single molecule level
Myosin-5B is an actin-based motor important for endosome recycling, but the molecular mechanism underlying its motility remains unknown. Here authors use single molecule imaging and high-speed laser tweezers to dissect the mechanoenzymatic properties of myosin-5B, which shows processive motility with peculiar mechanosensitivity.
- Lucia Gardini
- , Sarah M. Heissler
- & Marco Capitanio
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Article
| Open AccessNuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair
Following DNA damage, different processes come to action to aid repair. The authors here find that microtubule filaments within the cell nucleus capture and non-randomly mobilize damaged chromatin to mediate DNA repair.
- Roxanne Oshidari
- , Jonathan Strecker
- & Karim Mekhail
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Article
| Open AccessDiffusive tail anchorage determines velocity and force produced by kinesin-14 between crosslinked microtubules
Kinesin-14s, such as Ncd, interact with microtubules with their non-processive motor domains and their diffusive tail domains, but the influence of the tail domains on motor performance is not known. Here the authors show that tail domain slippage limits the velocities and forces generated by Ncd, suggesting it acts as a slippery crosslinker.
- Annemarie Lüdecke
- , Anja-Maria Seidel
- & Stefan Diez
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Article
| Open AccessFrequent pauses in Escherichia coli flagella elongation revealed by single cell real-time fluorescence imaging
The bacterial flagellar filament is assembled from tens of thousands of flagellin subunits that are exported by a dedicated secretion system. Here, the authors show that, on average, the growth rate of flagella in E. coli decays as flagella lengthen, with large variations due to frequent pauses.
- Ziyi Zhao
- , Yifan Zhao
- & Fan Bai
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Article
| Open AccessBayesian model selection for complex dynamic systems
Systematic changes in stock market prices or in the migration behaviour of cancer cells may be hidden behind random fluctuations. Here, Mark et al. describe an empirical approach to identify when and how such real-world systems undergo systematic changes.
- Christoph Mark
- , Claus Metzner
- & Ben Fabry
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Article
| Open AccessCryo-EM reveals the structural basis of microtubule depolymerization by kinesin-13s
Kinesin-13s are microtubule depolymerases that lack motile activity. Here the authors present the cryo-EM structures of kinesin-13 microtubule complexes in different nucleotide bound states, which reveal how ATP hydrolysis is linked to conformational changes and propose a model for kinesin induced depolymerisation.
- Matthieu P.M.H. Benoit
- , Ana B. Asenjo
- & Hernando Sosa
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Article
| Open AccessInstability of expanding bacterial droplets
Sokolov et al. have previously shown how bacteria are expelled in response to a rotating microparticle. Here the authors find that when the microparticle is spun at much higher rotation rates bacteria are trapped around it and then are expelled radially upon rotation cessation in an explosion-like manner.
- Andrey Sokolov
- , Leonardo Dominguez Rubio
- & Igor S. Aranson
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Article
| Open AccessThe preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor
Land plants lack the cytoplasmic dynein motor in fungi and animals that shows processive minus-end-directed motility on microtubules. Here the authors demonstrate that land plants have evolved novel processive minus-end-directed kinesin-14 motors that likely compensate for the absence of dynein.
- Kuo-Fu Tseng
- , Pan Wang
- & Weihong Qiu
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Article
| Open AccessUncovering the balance of forces driving microtubule aster migration in C. elegans zygotes
Microtubule asters are positioned precisely within cells by forces generated by molecular motors, but it is unclear how these are integrated in space and time. Here the authors perform in vivo drag measurements and genetic manipulations to determine the balance of forces that position microtubule asters in C. elegans zygotes.
- A. De Simone
- , A. Spahr
- & P. Gönczy
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Article
| Open AccessProtein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes
Protein phosphatase 5 (PP5) is expressed in many cell types but its role in cardiomyocytes is unknown. Here the authors show that PP5 binds and dephosphorylates elastic titin in cardiac sarcomeres, and that PP5 is increased in heart failure, reducing cardiomyocyte compliance.
- Judith Krysiak
- , Andreas Unger
- & Wolfgang A. Linke
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Article
| Open AccessThe opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
Marginal zone B (MZB) cells shuttle between the marginal zone and lymphoid follicle to capture and present peripheral blood antigens. Here the authors show that shear force, such as blood flow from the sinus around the follicle, is a directional cue that induces MZB migration on ICAM-1, and that S1P signaling inhibits this directional migration.
- Kerry Tedford
- , Michael Steiner
- & Klaus-Dieter Fischer
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Article
| Open AccessActive diffusion and advection in Drosophila oocytes result from the interplay of actin and microtubules
Intracellular transport is facilitated by a combination of processes including directed transport, advection and diffusion. Here the authors microscopically characterise the dynamics of the Drosophila oocyte and find distinct contributions of cytoskeletal components to advection and active diffusion.
- Maik Drechsler
- , Fabio Giavazzi
- & Isabel M. Palacios
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Article
| Open AccessEmergent patterns of collective cell migration under tubular confinement
Collective epithelial behaviours are studied in vitro in the context of flat sheets but a system to mimic tubular systems is lacking. Here, the authors develop a method to study collective behaviour in lumenal structures and show that several features depend on the extent of tubular confinement and/or curvature.
- Wang Xi
- , Surabhi Sonam
- & Chwee Teck Lim
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Article
| Open AccessHuman sperm steer with second harmonics of the flagellar beat
The mechanism allowing sperm to steer is not fully understood. The authors find that superposition of two harmonic waves breaks the flagellar beat symmetry temporally rather than spatially, and that this mechanism is enhanced by the sexual hormone progesterone, which changes the motility pattern.
- Guglielmo Saggiorato
- , Luis Alvarez
- & Jens Elgeti
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Article
| Open AccessA structural model of flagellar filament switching across multiple bacterial species
Bacterial flagellar filaments are composed almost entirely of a single protein—flagellin—which can switch between different supercoiled states in a highly cooperative manner. Here the authors present near-atomic resolution cryo-EM structures of nine flagellar filaments, and begin to shed light on the molecular basis of filament switching.
- Fengbin Wang
- , Andrew M. Burrage
- & Edward H. Egelman
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Article
| Open AccessMyosin Va molecular motors manoeuvre liposome cargo through suspended actin filament intersections in vitro
Cellular cargo transported along actin filaments is faced with a directional choice at an intersection. Here the authors show that myosin Va-bound cargo prefers to go straight through the intersection, and propose a model to explain this by a tug-of-war between motors on the lipid cargo that engage the actin tracks.
- Andrew T. Lombardo
- , Shane R. Nelson
- & David M. Warshaw
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Article
| Open AccessShifting the optimal stiffness for cell migration
Cell migration is sensitive to environmental stiffness, but how cells sense optimal stiffness is not known. Here the authors develop a model that predicts that the optimum can be shifted by altering the number of active molecular motors and clutches, and verify their model in two cell types.
- Benjamin L. Bangasser
- , Ghaidan A. Shamsan
- & David J. Odde
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Article
| Open AccessProbing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots
Methods to probe transport dynamics within cells can shed insight into the nature of the cytoplasm. Here the authors develop a method to functionalize and deliver quantum dots intracellularly to show how the cytoskeleton influences non-equilibrium intracellular transport dynamics.
- Eugene A. Katrukha
- , Marina Mikhaylova
- & Lukas C. Kapitein