Searcharxiv⌕ Search

arXiv subjects

F. C. MacKintosh

Publications and source records attributed to F. C. MacKintosh.

At least 19 recordsLinked to original sources
arXiv2020

Motor-free Contractility in Active Gels

Animal cells form contractile structures to promote various functions, from cell motility to cell division. Force generation in these structures is often due to molecular motors such as myosin that require polar substrates for their function. Here, we propose a motor-free mechanism that can generate contraction in biopolymer networks without the need for polarity. This mechanism is based on active binding/unbinding of crosslinkers that breaks the principle of detailed balance, together with the asymmetric force-extension response of semiflexible biopolymers. We find that these two ingredients can generate steady state contraction via a non-thermal, ratchet-like process. We calculate the resulting force-velocity relation using both coarse-grained and microscopic models.

physics.bio-ph↗
arXiv2019

Stress relaxation in F-actin solutions by severing

Networks of filamentous actin (F-actin) are important for the mechanics of most animal cells. These cytoskeletal networks are highly dynamic, with a variety of actin-associated proteins that control cross-linking, polymerization and force generation in the cytoskeleton. Inspired by recent rheological experiments on reconstituted solutions of dynamic actin filaments, we report a theoretical model that describes stress relaxation behavior of these solutions in the presence of severing proteins. We show that depending on the kinetic rates of assembly, disassembly, and severing, one can observe both length-dependent and length-independent relaxation behavior.

cond-mat.soft↗
arXiv2019

Origin of slow stress relaxation in the cytoskeleton

Dynamically crosslinked semiflexible biopolymers such as the actin cytoskeleton govern the mechanical behavior of living cells. Semiflexible biopolymers nonlinearly stiffen in response to mechanical loads, whereas the crosslinker dynamics allow for stress relaxation over time. Here we show, through rheology and theoretical modeling, that the combined nonlinearity in time and stress leads to an unexpectedly slow stress relaxation, similar to the dynamics of disordered systems close to the glass transition. Our work suggests that transient crosslinking combined with internal stress can explain prior reports of soft glassy rheology of cells, in which the shear modulus increases weakly with frequency.

cond-mat.soft↗
arXiv2018

Normal stresses in semiflexible polymer hydrogels

Biopolymer gels such as fibrin and collagen networks are known to develop tensile axial stress when subject to torsion. This negative normal stress is opposite to the classical Poynting effect observed for most elastic solids including synthetic polymer gels, where torsion provokes a positive normal stress. As recently shown, this anomalous behavior in fibrin gels depends on the open, porous network structure of biopolymer gels, which facilitates interstitial fluid flow during shear and can be described by a phenomenological two-fluid model with viscous coupling between network and solvent. Here we extend this model and develop a microscopic model for the individual diagonal components of the stress tensor that determine the axial response of semi-flexible polymer hydrogels. This microscopic model predicts that the magnitude of these stress components depends inversely on the characteristic strain for the onset of nonlinear shear stress, which we confirm experimentally by shear rheometry on fibrin gels. Moreover, our model predicts a transient behavior of the normal stress, which is in excellent agreement with the full time-dependent normal stress we measure.

cond-mat.soft↗
arXiv2016

Strain-driven criticality underlies nonlinear mechanics of fibrous networks

Networks with only central force interactions are floppy when their average connectivity is below an isostatic threshold. Although such networks are mechanically unstable, they can become rigid when strained. It was recently shown that the transition from floppy to rigid states as a function of simple shear strain is continuous, with hallmark signatures of criticality (Nat. Phys. 12, 584 (2016)). The nonlinear mechanical response of collagen networks was shown to be quantitatively described within the framework of such mechanical critical phenomenon. Here, we provide a more quantitative characterization of critical behavior in subisostatic networks. Using finite size scaling we demonstrate the divergence of strain fluctuations in the network at well-defined critical strain. We show that the characteristic strain corresponding to the onset of strain stiffening is distinct from but related to this critical strain in a way that depends on critical exponents. We confirm this prediction experimentally for collagen networks. Moreover, we find that the apparent critical exponents are largely independent of the spatial dimensionality. In a highly simplified computational model of network dynamics, we also observe critical slowing down in the vicinity of the critical strain. With subisostaticity as the only required condition, strain-driven criticality is expected to be a general feature of biologically relevant fibrous networks.

physics.bio-ph↗
arXiv2016

Broken Detailed Balance of Filament Dynamics in Active Networks

Myosin motor proteins drive vigorous steady-state fluctuations in the actin cytoskeleton of cells. Endogenous embedded semiflexible filaments such as microtubules, or added filaments such as single-walled carbon nanotubes are used as novel tools to non-invasively track equilibrium and non-equilibrium fluctuations in such biopolymer networks. Here we analytically calculate shape fluctuations of semiflexible probe filaments in a viscoelastic environment, driven out of equilibrium by motor activity. Transverse bending fluctuations of the probe filaments can be decomposed into dynamic normal modes. We find that these modes no longer evolve independently under non-equilibrium driving. This effective mode coupling results in non-zero circulatory currents in a conformational phase space, reflecting a violation of detailed balance. We present predictions for the characteristic frequencies associated with these currents and investigate how the temporal signatures of motor activity determine mode correlations, which we find to be consistent with recent experiments on microtubules embedded in cytoskeletal networks.

physics.bio-ph↗
arXiv2016

Critical behaviour in the nonlinear elastic response of hydrogels

In this paper we study the elastic response of synthetic hydrogels to an applied shear stress. The hydrogels studied here have previously been shown to mimic the behaviour of biopolymer networks when they are sufficiently far above the gel point. We show that near the gel point they exhibit an elastic response that is consistent with the predicted critical behaviour of networks near or below the isostatic point of marginal stability. This point separates rigid and floppy states, distinguished by the presence or absence of finite linear elastic moduli. Recent theoretical work has also focused on the response of such networks to finite or large deformations, both near and below the isostatic point. Despite this interest, experimental evidence for the existence of criticality in such networks has been lacking. Using computer simulations, we identify critical signatures in the mechanical response of sub-isostatic networks as a function of applied shear stress. We also present experimental evidence consistent with these predictions. Furthermore, our results show the existence of two distinct critical regimes, one of which arises from the nonlinear stretch response of semi-flexible polymers..

cond-mat.soft↗
arXiv2015

Multi-scale strain-stiffening of semiflexible bundle networks

Bundles of polymer filaments are responsible for the rich and unique mechanical behaviors of many biomaterials, including cells and extracellular matrices. In fibrin biopolymers, whose nonlinear elastic properties are crucial for normal blood clotting, protofibrils self-assemble and bundle to form networks of semiflexible fibers. Here we show that the extraordinary strain-stiffening response of fibrin networks is a direct reflection of the hierarchical architecture of the fibrin fibers. We measure the rheology of networks of unbundled protofibrils and find excellent agreement with an affine model of extensible wormlike polymers. By direct comparison with these data, we show that physiological fibrin networks composed of thick fibers can be modeled as networks of tight protofibril bundles. We demonstrate that the tightness of coupling between protofibrils in the fibers can be tuned by the degree of enzymatic intermolecular crosslinking by the coagulation Factor XIII. Furthermore, at high stress, the protofibrils contribute independently to the network elasticity, which may reflect a decoupling of the tight bundle structure. The hierarchical architecture of fibrin fibers can thus account for the nonlinearity and enormous elastic resilience characteristic of blood clots.

physics.bio-ph↗
arXiv2015

Strain-controlled criticality governs the nonlinear mechanics of fibre networks

Disordered fibrous networks are ubiquitous in nature as major structural components of living cells and tissues. The mechanical stability of networks generally depends on the degree of connectivity: only when the average number of connections between nodes exceeds the isostatic threshold are networks stable (Maxwell, J. C., Philosophical Magazine 27, 294 (1864)). Upon increasing the connectivity through this point, such networks undergo a mechanical phase transition from a floppy to a rigid phase. However, even sub-isostatic networks become rigid when subjected to sufficiently large deformations. To study this strain-controlled transition, we perform a combination of computational modeling of fibre networks and experiments on networks of type I collagen fibers, which are crucial for the integrity of biological tissues. We show theoretically that the development of rigidity is characterized by a strain-controlled continuous phase transition with signatures of criticality. Our experiments demonstrate mechanical properties consistent with our model, including the predicted critical exponents. We show that the nonlinear mechanics of collagen networks can be quantitatively captured by the predictions of scaling theory for the strain-controlled critical behavior over a wide range of network concentrations and strains up to failure of the material.

physics.bio-ph↗
arXiv2015

Anomalous discontinuity at the percolation critical point of active gels

We develop a percolation model motivated by recent experimental studies of gels with active network remodeling by molecular motors. This remodeling was found to lead to a critical state reminiscent of random percolation (RP), but with a cluster distribution inconsistent with RP. Our model not only can account for these experiments, but also exhibits an unusual type of mixed phase transition: We find that the transition is characterized by signatures of criticality, but with a discontinuity in the order parameter.

cond-mat.stat-mech↗
arXiv2015

Nonthermal Fluctuations of the Mitotic Spindle

We present direct measurements of fluctuations in the nucleus of yeast cells. While prior work has shown these fluctuations to be active and non-thermal in character, their origin and time dependence are not understood. We show that the nuclear fluctuations we observe are quantitatively consistent with uncorrelated, active force fluctuations driving a nuclear medium that is dominated by an uncondensed DNA solution, for which we perform rheological measurements on an {\it in vitro} model system under similar conditions to what is expected in the nucleus.

physics.bio-ph↗
arXiv2015

Driven diffusive systems with mutually interactive Langmuir kinetics

We investigate the simple one-dimensional driven model, the totally asymmetric exclusion process, coupled to mutually interactive Langmuir kinetics. This model is motivated by recent studies on clustering of motor proteins on microtubules. In the proposed model, the attachment and detachment rates of a particle are modified depending upon the occupancy of neighbouring sites. We first obtain continuum mean-field equations and in certain limiting cases obtain analytic solutions. We show how mutual interactions increase (decrease) the effects of boundaries on the phase behavior of the model. We perform Monte Carlo simulations and demonstrate that our analytical approximations are in good agreement with the numerics over a wide range of model parameters. We present phase diagrams over a selective range of parameters.

physics.bio-ph↗
arXiv2014

Active biopolymer networks generate scale-free but euclidean clusters

We report analytical and numerical modelling of active elastic networks, motivated by experiments on crosslinked actin networks contracted by myosin motors. Within a broad range of parameters, the motor-driven collapse of active elastic networks leads to a critical state. We show that this state is qualitatively different from that of the random percolation model. Intriguingly, it possesses both euclidean and scale-free structure with Fisher exponent smaller than $2$. Remarkably, an indistinguishable Fisher exponent and the same euclidean structure is obtained at the critical point of the random percolation model after absorbing all enclaves into their surrounding clusters. We propose that in the experiment the enclaves are absorbed due to steric interactions of network elements. We model the network collapse, taking into account the steric interactions. The model shows how the system robustly drives itself towards the critical point of the random percolation model with absorbed enclaves, in agreement with the experiment.

physics.bio-ph↗
arXiv2013

Elastic response of filamentous networks with compliant crosslinks

Experiments have shown that elasticity of disordered filamentous networks with compliant crosslinks is very different from networks with rigid crosslinks. Here, we model and analyze filamentous networks as a collection of randomly oriented rigid filaments connected to each other by flexible crosslinks that are modeled as worm-like chains. For relatively large extensions we allow for enthalpic stretching of crosslinks' backbones. We show that for sufficiently high crosslink density, the network linear elastic response is affine on the scale of the filaments' length. The nonlinear regime can become highly nonaffine and is characterized by a divergence of the elastic modulus at finite strain. In contrast to the prior predictions, we do not find an asymptotic regime in which the differential elastic modulus scales linearly with the stress, although an approximate linear dependence can be seen in a transition from entropic to enthalpic regimes. We discuss our results in light of the recent experiments.

physics.bio-ph↗
arXiv2012

Scale-dependent non-affine elasticity of semiflexible polymer networks

The cytoskeleton of eukaryotic cells provides mechanical support and governs intracellular transport. These functions rely on the complex mechanical properties of networks of semiflexible protein filaments. Recent theoretical interest has focused on mesoscopic properties of such networks and especially on the effect of local, non-affine bending deformations on mechanics. Here, we study the impact of local network deformations on the scale-dependent mobility of probe particles in entangled networks of semiflexible actin filaments by high-bandwidth microrheology. We find that micron-sized particles in these networks experience two opposing non-continuum elastic effects: entropic depletion reduces the effective network rigidity, while local non-affine deformations of the network substantially enhance the rigidity at low frequencies. We show that a simple model of lateral bending of filaments embedded in a viscoelastic background leads to a scaling regime for the apparent elastic modulus G'(ω) \sim ω^{9/16}, closely matching the experiments. These results provide quantitative evidence for how different a semiflexible polymer network can feel for small objects, and they demonstrate how non-affine bending deformations can be dominant for the mobility of vesicles and organelles in the cell.

cond-mat.soft↗
arXiv2012

Actively stressed marginal networks

We study the effects of motor-generated stresses in disordered three dimensional fiber networks using a combination of a mean-field, effective medium theory, scaling analysis and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of non-affine strain fluctuations as a susceptibility to motor stress.

physics.bio-ph↗
arXiv2011

Length-Controlled Elasticity in 3D Fiber Networks

We present a model for disordered 3D fiber networks to study their linear and nonlinear elasticity over a wide range of network densities and fiber lengths. In contrast to previous 2D models, these 3D networks with binary cross-links are under-constrained with respect to fiber stretching elasticity, suggesting that bending may dominate their response. We find that such networks exhibit a fiber length-controlled bending regime and a crossover to a stretch-dominated regime for lengths beyond a characteristic scale that depends on the fiber's elastic properties. Finally, by extending the model to the nonlinear regime, we show that these networks become intrinsically nonlinear with a vanishing linear response regime in the limit of floppy or long filaments.

cond-mat.soft↗