Cytoskeleton dynamics: Fluctuations within the network

Bursać, Predrag; Fabry, Ben; Trepat, Xavier; Lenormand, Guillaume; Butler, James P.; Wang, Ning; Fredberg, Jeffrey J.; An, Steven S.

doi:10.1016/j.bbrc.2007.01.191

Cited by 88 publications

(108 citation statements)

References 46 publications

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“…When mean square bead displacement (MSD) was resolved as a function of time lag ⌬t, it exhibited subdiffusive behavior for small ⌬t and superdiffusive behavior for large ⌬t (Fig. 3A), confirming many previous reports (4,26,27). With increasing volume fraction, there was a dramatic reduction in spontaneous bead motions, but even at the maximum volume fraction these motions remained superdiffusive at long time scales indicating persistent nonequilibrium dynamics in the crowded intracellular space (Fig.…”

Section: Resultssupporting

confidence: 88%

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition

Zhou¹,

Trepat

Park³

et al. 2009

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

256

245

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Mechanical robustness of the cell under different modes of stress and deformation is essential to its survival and function. Under tension, mechanical rigidity is provided by the cytoskeletal network; with increasing stress, this network stiffens, providing increased resistance to deformation. However, a cell must also resist compression, which will inevitably occur whenever cell volume is decreased during such biologically important processes as anhydrobiosis and apoptosis. Under compression, individual filaments can buckle, thereby reducing the stiffness and weakening the cytoskeletal network. However, the intracellular space is crowded with macromolecules and organelles that can resist compression. A simple picture describing their behavior is that of colloidal particles; colloids exhibit a sharp increase in viscosity with increasing volume fraction, ultimately undergoing a glass transition and becoming a solid. We investigate the consequences of these 2 competing effects and show that as a cell is compressed by hyperosmotic stress it becomes progressively more rigid. Although this stiffening behavior depends somewhat on cell type, starting conditions, molecular motors, and cytoskeletal contributions, its dependence on solid volume fraction is exponential in every instance. This universal behavior suggests that compressioninduced weakening of the network is overwhelmed by crowdinginduced stiffening of the cytoplasm. We also show that compression dramatically slows intracellular relaxation processes. The increase in stiffness, combined with the slowing of relaxation processes, is reminiscent of a glass transition of colloidal suspensions, but only when comprised of deformable particles. Our work provides a means to probe the physical nature of the cytoplasm under compression, and leads to results that are universal across cell type.T he abilities of the eukaryotic cell to maintain shape, flow, and remodel are mechanical attributes of substantial biological importance (1-5), but our understanding of how cellular constituents give rise to these mechanical attributes remains incomplete. Much of the mechanical rigidity of the cell comes from the cytoskeletal network, composed primarily of actin filaments, microtubules and intermediate filaments. The cytoskeletal network is predominantly under tension; its stiffness increases with tension and thereby increases the forces it can support (6-8). However, filamentous networks typically cannot support appreciable compressive stress because filaments will lose their tension, perhaps even buckle, and thus weaken the network. Nevertheless, cellular compression occurs within tumors (9) and will always occur if the volume of the cell is decreased, as occurs in important physiological processes such as osmotic cell shrinkage, regulatory cell volume decreases (10), preservation of certain animal life forms during drought (anhydrobiosis) (11), and apoptosis (12,13).In addition to containing the cytoskeletal network, the intracellular space is filled to near capacity with macrom...

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Section: Resultssupporting

confidence: 88%

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition

Zhou¹,

Trepat

Park³

et al. 2009

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

256

245

View full text Add to dashboard Cite

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“…Newman Stephens has suggested that asthmatic airway smooth muscle demonstrates more MLCK content and activity than that of normal airways (16,17). Certainly, in addition to the contractile apparatus, the actin cytoskeleton may play a role in regulating FFIR, as suggested by Lakser and Fredberg (4,33). Also, actomyosin crossbridge Figure 2.…”

Section: Discussionmentioning

confidence: 98%

“…Herrera and colleagues have demonstrated that associated actin (32) and myosin (25)(26)(27) filaments in TSM increase in length with contraction, and dynamically shorten and lengthen with airway smooth muscle cell migration (23,24). This dynamic nature of actin filament assembly and evanescence cannot be accounted for by the actin filamentstabilizing effects of such proteins as tropomyosin (29)(30)(31) or caldesmon (33,34). Therefore, we used pharmacologic tools to test the hypothesis that altering actin dynamics and therefore actin filament length would indeed modify FFIR of contracted airway smooth muscle.…”

Section: Actin Filament Length As a Regulator Of Ffirmentioning

confidence: 99%

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Mitchell¹,

Dowell²,

Solway³

et al. 2008

Proceedings of the American Thoracic Society

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Superimposition of force fluctuations on contracted tracheal smooth muscle (TSM) has been used to simulate normal breathing. Breathing has been shown to reverse lung resistance of individuals without asthma and animals given methacholine to contract their airways; computed tomography scans also demonstrated bronchial dilation after a deep inhalation in normal volunteers. This reversal of airway resistance and bronchial constriction are absent (or much diminished) in individuals with asthma. Many studies have demonstrated that superimposition of force oscillations on contracted airway smooth muscle results in substantial smooth muscle lengthening. Subsequent studies have shown that this force fluctuation-induced relengthening (FFIR) is a physiologically regulated phenomenon. We hypothesized that actin filament length in the smooth muscle of the airways regulates FFIR of contracted tissues. We based this hypothesis on the observations that bovine TSM strips contracted using acetylcholine (ACh) demonstrated amplitude-dependent FFIR that was sensitive to mitogen-activated protein kinase (p38 MAPK) inhibition-an upstream regulator of actin filament assembly. We demonstrated latrunculin B (sequesters actin monomers thus preventing their assimilation into filaments resulting in shorter filaments) greatly increases FFIR and jasplakinolide (an actin filament stabilizer) prevents the effects of latrunculin B incubation on strips of contracted canine TSM. We suspect that p38 MAPK inhibition and latrunculin B predispose to shorter actin filaments. These studies suggest that actin filament length may be a key determinant of airway smooth muscle relengthening and perhaps breathing-induced reversal of agonist-induced airway constriction. Keywords: actin filament length; latrunculin B; jasplakinolideMany studies have demonstrated that superimposition of force oscillations on contracted airway smooth muscle results in substantial smooth muscle lengthening in vitro (1-4), a phenomenon we refer to as force fluctuation-induced relengthening (FFIR). It has been proposed that imposition of these force oscillations simulate the effect of breathing on airway responsiveness and caliber. Shen and coworkers demonstrated in ventilated rabbits that breathing reduced methacholine-elicited airway resistance in a tidal volume-dependent manner (5). In normal individuals who demonstrated increased airway resistance to inhaled methacholine, the degree of bronchoconstriction could be reversed again by normal, tidal breathing (6, 7) or by taking a single deep inspiration (8-10). This airway dilation with deep inspiration also was demonstrated directly by looking at computed tomography (CT) scans of normal volunteers (8). Lung tethering forces on the conducting airways probably contributed to this dilation by loading the smooth muscle in the bronchiolar walls (8-10). However, this reversal of bronchoconstriction with breathing or deep inspiration is absent or minimal in individuals with asthma (9, 10); their airways remain constricted to methacholin...

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“…However, probe particles moving in heterogeneous active viscoelastic media can be transported in a variety of ways, so naively applying thermal fluctuation microrheology is usually inappropriate and can lead to a misinterpretation of the local mechanical properties. 8,[15][16][17][18] Over certain time scales, the MSD can sometimes be described by a time-dependent power law, 〈Δr 2 (t)〉∼t α , where the diffusive exponent, 19 α, can be related to the type of motion a particle is undergoing over a range of correlation times, t. The modes of probe motion observed are as follows: local elastic trapping (α≈0), sub-diffusion (α<1), diffusion (α=1), a combination of diffusion and convection (α>1), and ballistic motion (also known as pure convection) (α≅2). A combination of diffusion and convection can occur, for example, in thermally diffusing particles within a crawling cell.…”

Section: Particle Tracking In Living Cellsmentioning

confidence: 99%

Effects of cytoskeletal disruption on transport, structure, and rheology within mammalian cells

2007

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Quantification of cellular responses to stimuli is challenging. Cells respond to changing external conditions through internal structural and compositional and functional modifications, thereby altering their transport and mechanical properties. By properly interpreting particle-tracking microrheology, we evaluate the response of live cells to cytoskeletal disruption mediated by the drug nocodazole. Prior to administering the drug, the particles exhibit an apparently diffusive behavior that is actually a combination of temporally heterogeneous ballistic and caged motion. Selectively depolymerizing microtubules with the drug causes actively crawling cells to halt, providing a means for assessing drug efficacy, and making the caged motion of the probes readily apparent.

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Cytoskeleton dynamics: Fluctuations within the network

Cited by 88 publications

References 46 publications

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Effects of cytoskeletal disruption on transport, structure, and rheology within mammalian cells

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