Spatial cytoskeleton organization supports targeted intracellular transport

Hafner, Anne E.; Rieger, Heiko

doi:10.1101/189365

Cited by 8 publications

(12 citation statements)

References 63 publications

(102 reference statements)

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“…Because our aim was to translate the switching behavior of individual melanosomes at a single filament crossing to the intracellular organization of these organelles, we explicitly modeled cytoskeletal networks composed of individual actin and microtubule filaments. Such explicit modeling of filament networks has recently unmasked previously inaccessible theoretical aspects of intracellular transport (25)(26)(27)(28)(29)(30)(31), while effective, continuous models yielded first fundamental insights into cytoskeletondependent transport processes (32)(33)(34)(35)(36). In order to study the impact of interfilament switching on intracellular melanosome distribution in Xenopus melanophores, we varied the switching probabilities only, leaving the velocities of simulated melanosomes on the microtubule and actin networks unchanged.…”

Section: Crossingsmentioning

confidence: 99%

Molecular underpinnings of cytoskeletal cross-talk

Oberhofer

Reithmann

Spieler

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Cross-talk between the microtubule and actin networks has come under intense scrutiny following the realization that it is crucial for numerous essential processes, ranging from cytokinesis to cell migration. It is becoming increasingly clear that proteins long-considered highly specific for one or the other cytoskeletal system do, in fact, make use of both filament types. How this functional duality of “shared proteins” has evolved and how their coadaptation enables cross-talk at the molecular level remain largely unknown. We previously discovered that the mammalian adaptor protein melanophilin of the actin-associated myosin motor is one such “shared protein,” which also interacts with microtubules in vitro. In a hypothesis-driven in vitro and in silico approach, we turn to early and lower vertebrates and ask two fundamental questions. First, is the capability of interacting with microtubules and actin filaments unique to mammalian melanophilin or did it evolve over time? Second, what is the functional consequence of being able to interact with both filament types at the cellular level? We describe the emergence of a protein domain that confers the capability of interacting with both filament types onto melanophilin. Strikingly, our computational modeling demonstrates that the regulatory power of this domain on the microscopic scale alone is sufficient to recapitulate previously observed behavior of pigment organelles in amphibian melanophores. Collectively, our dissection provides a molecular framework for explaining the underpinnings of functional cross-talk and its potential to orchestrate the cell-wide redistribution of organelles on the cytoskeleton.

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Section: Crossingsmentioning

confidence: 99%

Molecular underpinnings of cytoskeletal cross-talk

Oberhofer

Reithmann

Spieler

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Their entirely biological nature makes them ideal for one‐time use applications and as clean, biodegradable alternatives to synthetic gels (Gong, Nitta, & Osada, ). Additionally, further research on this structure type will advance the basic science of active materials, ultimately helping scientists and engineers develop new quantitative models of stress fluctuations in materials out of equilibrium (Brangwynne, Koenderink, MacKintosh, & Weitz, ) and transport properties of such materials (Hafner & Rieger, ), for example.…”

Section: Gliding Assays: the First Motile Engineered Biological Micromentioning

confidence: 99%

From isolated structures to continuous networks: A categorization of cytoskeleton‐based motile engineered biological microstructures

Andorfer

Alper

2019

WIREs Nanomed Nanobiotechnol

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As technology at the small scale is advancing, motile engineered microstructures are becoming useful in drug delivery, biomedicine, and lab-on-a-chip devices. However, traditional engineering methods and materials can be inefficient or functionally inadequate for small-scale applications. Increasingly, researchers are turning to the biology of the cytoskeleton, including microtubules, actin filaments, kinesins, dyneins, myosins, and associated proteins, for both inspiration and solutions. They are engineering structures with components that range from being entirely biological to being entirely synthetic mimics of biology and on scales that range from isotropic continuous networks to single isolated structures. Motile biological microstructures trace their origins from the development of assays used to study the cytoskeleton to the array of structures currently available today. We define 12 types of motile biological microstructures, based on four categories: entirely biological, modular, hybrid, and synthetic, and three scales: networks, clusters, and isolated structures. We highlight some key examples, the unique functionalities, and the potential applications of each microstructure type, and we summarize the quantitative models that enable engineering them. By categorizing the diversity of motile biological microstructures in this way, we aim to establish a framework to classify these structures, define the gaps in current research, and spur ideas to fill those gaps. active matter, biomimicry, biomolecular motor protein, cytoskeletal networks, microscale devicesThe challenges of biomedical research and development often lie at the interface between the medical intervention and the biological material. The relevant scale of this interface is on the order of nanometers (molecular scale) or smaller for drug developers, and the relevant scale of this interface is on the order of millimeters (tissue scale) or larger for biomedical device designers. However, there is an emerging class of biomedical solutions with scale on the order of micrometers (cellular scale).

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“…The stochastic attachment and detachment of molecular motors to and from the filaments combined with intermittent diffusion of the detached motors can mathematically be described by an intermittent search process [3,4], alternating randomly between a cytoplasmic diffusive transport and a ballistic transport on filaments [5]. Recently, it was shown the transport time to reach a specific area, the escape area, on the cell membrane by this intermittent search can be minimized with respect to the cortex width [6][7][8][9] due to an accelerated effective diffusion close to the cell membrane and the efficiency of the intermittent search. For small typical size ε of the escape area, this intracellular transport constitutes the narrow escape problem (NEP) in a spatially inhomogeneous environment.…”

Section: Introductionmentioning

confidence: 99%

Narrow escape problem in two-shell spherical domains

Mangeat,

Rieger

2021

Preprint

Self Cite

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Intracellular transport in living cells is often spatially inhomogeneous with an accelerated effective diffusion close to the cell membrane and a ballistic motion away from the centrosome due to active transport along actin filaments and microtubules, respectively. Recently it was reported that the mean first passage time (MFPT) for transport to a specific area on the cell membrane is minimal for an optimal actin cortex width. In this paper we ask whether this optimization in a two-compartment domain can also be achieved by passive Brownian particles. We consider a Brownian motion with different diffusion constants in the two shells and a potential barrier between the two and investigate the narrow escape problem by calculating the MFPT for Brownian particles to reach a small window on the external boundary. In two and three dimensions, we derive asymptotic expressions for the MFPT in the thin cortex and small escape region limits confirmed by numerical calculations of the MFPT using the finite element method and stochastic simulations. From this analytical and numeric analysis we finally extract the dependence of the MFPT on the ratio of diffusion constants, the potential barrier height and the width of the outer shell. The first two are monotonous whereas the last one may have a minimum for a sufficiently attractive cortex, for which we propose an analytical expression of the potential barrier height matching very well the numerical predictions.

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Spatial cytoskeleton organization supports targeted intracellular transport

Cited by 8 publications

References 63 publications

Molecular underpinnings of cytoskeletal cross-talk

Molecular underpinnings of cytoskeletal cross-talk

From isolated structures to continuous networks: A categorization of cytoskeleton‐based motile engineered biological microstructures

Narrow escape problem in two-shell spherical domains

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