Intracellular Fluid Mechanics: Coupling Cytoplasmic Flow with Active Cytoskeletal Gel

Mogilner, Alex; Manhart, Angelika

doi:10.1146/annurev-fluid-010816-060238

Cited by 96 publications

(104 citation statements)

References 133 publications

(181 reference statements)

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“…The subset of constraints which are both generative and dependent is then C2, C3, and C4. According to Montévil et al [23] the organization constituted by C2, C3, and C4 realizes closure.…”

Section: Constraints Confer An Additional Level Of Causation In Self-mentioning

confidence: 99%

“…Contrary to the a critical belief that molecules can freely move in the cytosol (the liquid component of the cytoplasm) according to Fick's diffusion law, it turns out that molecules diffusivity is a complex, only partially understood phenomenon. [ 23 ] Indeed, the motility of molecules is highly constrained by the colloid‐like nature of the cytosol as well as by the intricate geometry of cytoskeletal networks and internal membranes, which causes the space available for diffusion in cytoplasm to be highly reduced and convoluted. [ 24 ] According to this example, constraints exert a strong effect on the observed phenomenon by channeling the motion along predefined tracks.…”

Section: What We Mean By the Concept Of “Constraint”mentioning

confidence: 99%

“…An intriguing case in point is provided by investigating how a classical, purely physical constraint like gravity, could dramatically influence cell differentiation and behavior. Classical physics posits that gravity will not cause any changes in cells because gravity is an extremely low force (10 1 versus 10 23 ) when compared to other physical forces acting on/within cells. [75] In principle, gravity should be unable in interfering with intraand intermolecular dynamics.…”

Section: Absence Of Gravity Deprives the Systems Of Directionality Inmentioning

confidence: 99%

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Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape

et al. 2020

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Studies performed in absence of gravitational constraint show that a living system is unable to choose between two different phenotypes, thus leading cells to segregate into different, alternative stable states. This finding demonstrates that the genotype does not determine by itself the phenotype but requires additional, physical constraints to finalize cell differentiation. Constraints belong to two classes: holonomic (independent of the system's dynamical states, as being established by the space‐time geometry of the field) and non‐holonomic (modified during those biological processes to which they contribute in shaping). This latter kind of “constraints”, in which dynamics works on the constraint to recreate them, have emerged as critical determinants of self‐organizing systems, by manifesting a “closure of constraints.” Overall, the constraints act by harnessing the “randomness” represented by the simultaneous presence of equiprobable events restraining the system within one attractor. These results cast doubt on the mainstream scientific concept and call for a better understanding of causation in cell biology.

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Section: Constraints Confer An Additional Level Of Causation In Self-mentioning

confidence: 99%

Section: What We Mean By the Concept Of “Constraint”mentioning

confidence: 99%

Section: Absence Of Gravity Deprives the Systems Of Directionality Inmentioning

confidence: 99%

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Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape

et al. 2020

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“…On the one hand, actomyosin networks crosslinked by a-actinin and other crosslinking proteins are able to adapt external forces via fast mechanical response; the mechanical stress relaxation occurs on the timescale of seconds (23)(24)(25)(26). On the other hand, cytoskeletal reactions, such as myosin activation, continuously convert biochemical energy into mechanical force; remodeling of the actin networks takes place on the time scale of minutes (27)(28)(29). As a result of myosin dominant mechanochemical dynamics, actin networks tend to contract (30,31).…”

Section: Introductionmentioning

confidence: 99%

Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry

et al. 2020

Preprint

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Understanding cellular remodeling in response to mechanical stimuli is a critical step in elucidating mechano-activation of biochemical signaling pathways. Experimental evidence indicates that external stress-induced subcellular adaptation is accomplished through dynamic cytoskeletal reorganization. To study the interactions between subcellular structures involved in transducing mechanical signals, we combined experimental and computational simulations to evaluate real-time mechanical adaptation of the actin cytoskeletal network. Actin cytoskeleton was imaged at the same time as an external tensile force was applied to live vascular smooth muscle cells using a fibronectin-functionalized atomic force microscope probe. In addition, we performed computational simulations of active cytoskeletal networks under a tensile external force. The experimental data and simulation results suggest that mechanical structural adaptation occurs before chemical adaptation during filament bundle formation: actin filaments first align in the direction of the external force, initializing anisotropic filament orientations, then the chemical evolution of the network follows the anisotropic structures to further develop the bundle-like geometry. This finding presents an alternative, novel explanation for the stress fiber formation and provides new insight into the mechanism of mechanotransduction. Author SummaryRemodeling the cytoskeletal network in response to external force is key to mechanosensing and locomotion. Despite much focus on cytoskeletal remodeling in recent years, a comprehensive understanding of actin remodeling in real-time in cells under mechanical stimuli is still lacking. We integrated stress-induced 3D actin imaging and 3D computational simulations of actin cytoskeleton to study how the actin cytoskeleton form bundles and how these bundles evolve over time upon external tensile stress. We found a rapid actin alignment and a slower bundle evolution leading to denser bundles. Based on these results, we propose a "mechanics before chemistry" model of actin cytoskeleton remodeling under external force.

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“…27 To highlight the potential importance of the hydrodynamics of extracellular fluid at 28 an interface, we perform a preliminary calculation (unrealistically) assuming cells are 29 rigid, impermeable spheres of radius r cell . In order to bring these cells into close contact, 30 a force F pushes them together, as shown in Fig. 1A.…”

Section: Introduction 16mentioning

confidence: 99%

Hydrodynamics of transient cell-cell contact: The role of membrane permeability and active protrusion length

Chu

Newby

et al. 2018

Preprint

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In many biological settings, two or more cells come into physical contact to form a cell-cell interface. In some cases, the cell-cell contact must be transient, forming on timescales of seconds. One example is offered by the T cell, an immune cell which must attach to the surface of other cells in order to decipher information about disease. The aspect ratio of these interfaces (tens of nanometers thick and tens of micrometers in diameter) puts them into the thin-layer limit, or "lubrication limit", of fluid dynamics. A key question is how the receptors and ligands on opposing cells come into contact. What are the relative roles of thermal undulations of the plasma membrane and deterministic forces from active filopodia? We use a computational fluid dynamics algorithm capable of simulating 10-nanometer-scale fluid-structure interactions with thermal fluctuations up to seconds-and microns-scales. We use this to simulate two opposing membranes, variously including thermal fluctuations, active forces, and membrane permeability. In some regimes dominated by thermal fluctuations, proximity is a rare event, which we capture by computing mean first-passage times using a Weighted Ensemble rare-event computational method. Our results demonstrate that the time-to-contact increases for smaller cell-cell distances (where the thin-layer effect is strongest), leading to an optimal initial cell-cell separation for fastest receptor-ligand binding. We reproduce a previous experimental observation that fluctuation spatial scales are largely unaffected, but timescales are dramatically slowed, by the thin-layer effect. We also find that membrane permeability would need to be above physiological levels to abrogate the thin-layer effect. Author summaryThe elastohydrodynamics of water in and around cells is playing an increasingly recognized . CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/367987 doi: bioRxiv preprint first posted online Jul. 12, 2018; can interact. To overcome the computational challenges associated with simulating fluid 5 in this mechanically soft, stochastic and high-aspect-ratio environment, we extend a 6 computational framework where the cell plasma membranes are treated as immersed 7 boundaries in the fluid, and combine this with computational methods for simulating 8 stochastic rare events in which an ensemble of simulations are given weights according 9 to their probability. We find that the internal dynamics of the membranes has speeds 10 in approximately microseconds, but that as the cells approach, a new slow timescale 11 of approximately milliseconds is introduced. Thermal undulations nor typical amounts 12 of membrane permeability can overcome the timescale, but active forces, e.g., from 13 the cytoskeleton, can. Our results suggest an explanation for differences in molecular 14 interactions i...

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Intracellular Fluid Mechanics: Coupling Cytoplasmic Flow with Active Cytoskeletal Gel

Cited by 96 publications

References 133 publications

Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape

Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape

Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry

Hydrodynamics of transient cell-cell contact: The role of membrane permeability and active protrusion length

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