Publications (43)58.1 Total impact
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ABSTRACT: Cells must move through tissues in many important biological processes, including embryonic development, cancer metastasis, and wound healing. In these tissues, a cell's motion is often strongly constrained by its neighbors, leading to glassy dynamics. Recent work has demonstrated the existence of a nonequilibrium glass transition in selfpropelled particle models for active matter, where the transition is driven by changes in density. However, this may not explain liquidtosolid transitions in confluent tissues, where there are no gaps between cells and the packing fraction remains fixed and equal to unity. Here we demonstrate the existence of a different type of glass transition that occurs in the wellstudied vertex model for confluent tissue monolayers. In this model, the onset of rigidity is governed by changes to singlecell properties such as cellcell adhesion, cortical tension, and volume compressibility, providing an explanation for a liquidtosolid transitions in confluent tissues.09/2014;  [Show abstract] [Hide abstract]
ABSTRACT: We construct and analyze a model for a disordered linear spring network with anisotropy. The modeling is motivated by, for example, granular systems, nematic elastomers, and ultimately cytoskeletal networks exhibiting some underlying anisotropy. The model consists of a triangular lattice with two different bond occupation probabilities, $p_x$ and $p_y$, for the linear springs. We develop an effective medium theory (EMT) to describe the network elasticity as a function of $p_x$ and $p_y$. We find that the onset of rigidity in the EMT agrees with Maxwell constraint counting. We also find beyond linear behavior in the shear and bulk modulus as a function of occupation probability in the rigid phase for small strains, which differs from the isotropic case. We compare our EMT with numerical simulations to find rather good agreement. Finally, we discuss the implications of extending the reach of effective medium theory as well as draw connections with prior work on both anisotropic and isotropic spring networks.08/2014;  [Show abstract] [Hide abstract]
ABSTRACT: Experiments suggest that the migration of some cells in the threedimensional extra cellular matrix bears strong resemblance to onedimensional cell migration. Motivated by this observation, we construct and study a minimal onedimensional model cell made of two beads and an active spring moving along a rigid track. The active spring models the stress fibers with their myosindriven contractility and alphaactinindriven extendability, while the friction coefficients of the two beads describe the catch/slip bond behavior of the integrins in focal adhesions. In the absence of active noise, net motion arises from an interplay between active contractility (and passive extendability) of the stress fibers and an asymmetry between the front and back of the cell due to catch bond behavior of integrins at the front of the cell and slip bond behavior of integrins at the back. We obtain reasonable cell speeds with independently estimated parameters. We also study the effects of hysteresis in the active spring, due to catch bond behavior and the dynamics of crosslinking, and the addition of active noise on the motion of the cell. Our model highlights the role of alphaactinin in threedimensional cell motility and does not require Arp2/3 actin filament nucleation for net motion.Physical review. E, Statistical, nonlinear, and soft matter physics. 06/2014; 90(31).  [Show abstract] [Hide abstract]
ABSTRACT: Recent observations demonstrate that confluent tissues exhibit features of glassy dynamics, such as caging behavior and dynamical heterogeneities, although it has remained unclear how singlecell properties control this behavior. Here we develop numerical and theoretical models to calculate energy barriers to cell rearrangements, which help govern cell migration in cell monolayers. In contrast to work on sheared foams, we find that energy barrier heights are exponentially distributed and depend systematically on the cell's number of neighbors. Based on these results, we predict glassy twotime correlation functions for cell motion, with a timescale that increases rapidly as cell activity decreases. These correlation functions are used to construct simple random walks that reproduce the caging behavior observed for cell trajectories in experiments. This work provides a theoretical framework for predicting collective motion of cells in woundhealing, embryogenesis and cancer tumorogenesis.Soft Matter 02/2014; 10(12):188590. · 4.15 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: We revisit the concept of minimal rigidity as applied to frictionless, repulsive soft sphere packings in two dimensions with the introduction of the jamming graph. Minimal rigidity is a purely combinatorial property encoded via Laman's theorem in two dimensions. It constrains the global, average coordination number of the graph, for example. However, minimal rigidity does not address the geometry of local mechanical stability. The jamming graph contains both properties of global mechanical stability at the onset of jamming and local mechanical stability. We demonstrate how jamming graphs can be constructed using local moves via the Henneberg construction such that these graphs fall under the jurisdiction of correlated percolation. We then probe how jamming graphs destabilize, or become unjammed, by deleting a bond and computing the resulting rigid cluster distribution. We also study how the system restabilizes with the addition of new contacts and how a jamming graph with extra (redundant) contacts destabilizes. The latter endeavor allows us to probe a disk packing in the rigid phase and uncover a potentially new diverging length scale associated with the random deletion of contacts as compared to the study of cutout (or frozenin) subsystems.Physical Review E 12/2013; 88(61):062130. · 2.31 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: During endocytosis, the cell membrane deforms to surround extracellular material and draw it into the cell. Experiments on clathrinmediated endocytosis in yeast all agree that (i) actin polymerizes into a network of filaments exerting active forces on the membrane to deform it and (ii) the large scale membrane deformation is tubular in shape. Three competing ideas remain as to precisely how the actin filament network organizes itself to drive the deformation. To begin to address this issue, we use variational approaches and numerical simulations to analyze a mesoscale model of clathrinmediated endocytosis in yeast. The mesoscale model breaks up the invagination process into three stages: (i) the initiation stage, where clathrin interacts with the membrane, (ii) the elongation stage, where the membrane is then pulled and/or squeezed via polymerizing actin filaments, followed by a (iii) final pinchoff stage. Our results suggest that the pinchoff mechanism is assisted by a pearlinglike instability. In addition, we potentially rule out two of the three competing models for the organization of the actin filament network during the elongation stage. These two models could possibly be important in the pinchoff stage, however, where actin polymerization helps break off the vesicle. Implications and comparisons with earlier modeling of clathrinmediated endocytosis in yeast is discussed.10/2013;  [Show abstract] [Hide abstract]
ABSTRACT: At the leading edge of a crawling cell, the actin cytoskeleton extends itself in a particular direction via a branched crosslinked network of actin filaments with some overall alignment. This network is known as the lamellipodium. Branching via the complex Arp2/3 occurs at a reasonably welldefined angle of 70 degrees from the plus end of the mother filament such that Arp2/3 can be modeled as an angleconstraining crosslinker. Freelyrotating crosslinkers, such as alphaactinin, are also present in lamellipodia. Therefore, we study the interplay between these two types of crosslinkers, angleconstraining and freerotating, both analytically and numerically, to begin to quantify the mechanics of lamellipodia. We also investigate how the orientational ordering of the filaments affects this interplay. Finally, while role of Arp2/3 as a nucleator for filaments along the leading edge of a crawling cell has been studied intensely, much less is known about its mechanical contribution. Our work seeks to fill in this important gap in modeling the mechanics of lamellipodia.03/2013;  [Show abstract] [Hide abstract]
ABSTRACT: The behavior of cellular aggregates strongly influences morphogenesis, cancer growth and wound healing. While single cell mechanics has been extensively studied, the collective dynamics of cells inside a tissue is not well understood. Recent experiments have shown cells in tissues behave like fluids on long timescales and solids on shorter timescales, and exhibit caging behavior at intermediate timescales as they are more tightly packed. These observations are reminiscent of dynamic slowing down and dynamical heterogeneities due to mutual confinement and crowding of particles glassy systems. A common and crucial feature of glassy systems is the existence of a Potential Energy Landscape (PEL) for local rearrangements. For thermal glassy materials, when these barriers are large compared to thermal fluctuations, its rheology is dependent on the PEL and external mechanical driving. In contrast, cells in a tissue are nonthermal and overcome energy barriers in the PEL mainly through local active processes, i.e. making new adhesions and cell shape changes. We numerically map the PEL of a confluent tissue as functions of different transition pathways and single cell properties. Analytical calculations are also performed to find the minimal energy shapes for 2D confluent cell packings.03/2013;  [Show abstract] [Hide abstract]
ABSTRACT: Cell migration is integral to several physiological processes such as immune response, wound healing, tissue formation, fertilization etc. Previous studies, both theoretical and experimental, have attempted to model different aspects of cell migration, including adhesion, protrusion and retraction at the level of single cells, and collective motion at the multicellular level. The entire motility process of a single cell and its ability to navigate a landscape containing obstacles is, however, not well understood. We attempt to address this issue by modeling a single moving cell as a Brownian inchworm composed of two beads attached by a spring that can sense and respond to the mechanical properties and architecture of its environment. The elastic interaction between inchworm and the substrate is modeled by molecular clutches. We study the dynamics of this inchworm in a corrugated potential. In particular we focus on the interplay between confinement and adhesion in the motility of this inchworm. This model may provide important insights on cell movement through a biological maze of other cellular and extracellular structures.03/2013;  [Show abstract] [Hide abstract]
ABSTRACT: In Bayın's paper [J. Math. Phys. 53, 042105 (2012)], he claims to prove the consistency of the purported piecewise solutions to the fractional Schrödinger equation for an infinite square well. However, his calculation uses standard contour integral techniques despite the absence of an analytic integrand. The correct calculation is presented and supports our earlier work proving that the purported piecewise solutions do not solve the fractional Schrödinger equation for an infinite square well [M. Jeng, S.L.Y. Xu, E. Hawkins, and J. M. Schwarz, J. Math. Phys. 51, 062102 (2010)].Journal of Mathematical Physics. 01/2013; 54(1):4101.  [Show abstract] [Hide abstract]
ABSTRACT: The recent proliferation of correlated percolation modelsmodels where the addition of edges and/or vertices is no longer independent of other edges and/or verticeshas been motivated by the quest to find discontinuous percolation transitions. The leader in this proliferation is what is known as explosive percolation. A recent proof demonstrates that a large class of explosive percolationtype models does not, in fact, exhibit a discontinuous transition [Riordan and Warnke, Science, 333, 322 (2011)]. Here, we discuss two lesser known correlated percolation modelsthe k≥3core model on random graphs and the counterbalance model in twodimensionsboth exhibiting discontinuous transitions. To search for tricriticality, we construct mixtures of these models with other percolation models exhibiting the more typical continuous transition. Using a powerful rate equation approach, we demonstrate that a mixture of k=2core and k=3core vertices on the random graph exhibits a tricritical point. However, for a mixture of kcore and counterbalance vertices in two dimensions, as the fraction of counterbalance vertices is increased, numerics and heuristic arguments suggest that there is a line of continuous transitions with the line ending at a discontinuous transition, i.e., when all vertices are counterbalanced. Interestingly, these heuristic arguments may help identify the ingredients needed for a discontinuous transition in low dimensions. In addition, our results may have potential implications for glassy and jamming systems.Physical Review E 12/2012; 86(61):061131. · 2.31 Impact Factor 
Article: Comment on: "On the consistency of solutions of the space fractional Schr\"odinger equation"
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ABSTRACT: In [J. Math. Phys. 53, 042105 (2012)], Bay{\i}n claims to prove the consistency of the purported piecewise solutions to the fractional Schr\"odinger equation for an infinite square well. However, his calculation uses standard contour integral techniques despite the absence of an analytic integrand. The correct calculation is presented and supports our earlier work proving that the purported piecewise solutions do not solve the fractional Schr\"odinger equation for an infinite square well [M. Jeng, S.L.Y. Xu, E. Hawkins, and J. M. Schwarz, J. Math. Phys. 51, 062102 (2010)].10/2012;  [Show abstract] [Hide abstract]
ABSTRACT: At the leading edge of a crawling cell, the actin cytoskeleton extends itself via a branched, crosslinked network of filaments, otherwise known as the lamellipodium. The filaments in this network have an average preferred orientation of around ± 30 degrees with respect to the normal of the leading edge. This preferred orientation of filaments leads to a material that is structurally anisotropic. To better understand the forces generated by the lamellipodium, we analytically and numerically study the mechanical properties of a model branched and crosslinked filamentous network where the filaments are preferentially oriented along one direction. We investigate the interplay between geometry, elasticity and anisotropy in the network. In particular, we show how anisotropy modulates the onset of rigidity and nonlinear mechanical response of the network.02/2012;  [Show abstract] [Hide abstract]
ABSTRACT: While the frictionless jamming transition has been intensely studied in recent years, more realistic frictional packings are less well understood. In frictionless sphere packings, the transition is predicted by a simple meanfield constraint counting argument, the isostaticity argument. For frictional packings, a modified constraint counting argument, which includes slipping contacts at the Coulomb threshold, has had limited success in accounting for the transition. We propose that the frictional jamming transition is not mean field and is triggered by the nucleation of unstable regions, which are themselves dynamical objects due to the Coulomb criterion. We create frictional packings using MD simulations and test for the presence and shape of rigid clusters with the pebble game to identify the partition of the packing into stable and unstable regions. To understand the dynamics of these unstable regions we follow perturbations at contacts crucial to the stability of the ``frictional house of cards.''02/2012; 
Article: Redundancy and cooperativity in the mechanics of compositely crosslinked filamentous networks.
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ABSTRACT: The cytoskeleton of living cells contains many types of crosslinkers. Some crosslinkers allow energyfree rotations between filaments and others do not. The mechanical interplay between these different crosslinkers is an open issue in cytoskeletal mechanics. Therefore, we develop a theoretical framework based on rigidity percolation to study a generic filamentous system containing both stretching and bondbending forces to address this issue. The framework involves both analytical calculations via effective medium theory and numerical simulations on a percolating triangular lattice with very good agreement between both. We find that the introduction of angleconstraining crosslinkers to a semiflexible filamentous network with freely rotating crosslinks can cooperatively lower the onset of rigidity to the connectivity percolation thresholda result argued for years but never before obtained via effective medium theory. This allows the system to ultimately attain rigidity at the lowest concentration of material possible. We further demonstrate that introducing angleconstraining crosslinks results in mechanical behaviour similar to just freely rotating crosslinked semflexible filaments, indicating redundancy and universality. Our results also impact upon collagen and fibrin networks in biological and bioengineered tissues.PLoS ONE 01/2012; 7(5):e35939. · 3.53 Impact Factor 
Article: Vicious accelerating walkers
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ABSTRACT: A vicious walker system consists of N random walkers on a line with any two walkers annihilating each other upon meeting. We study a system of N vicious accelerating walkers with the velocity undergoing Gaussian fluctuations, as opposed to the position. We numerically compute the survival probability exponent, {\alpha}, for this system, which characterizes the probability for any two walkers not to meet. For example, for N = 3, {\alpha} = 0.71 \pm 0.01. Based on our numerical data, we conjecture that 1/8N(N  1) is an upper bound on {\alpha}. We also numerically study N vicious Levy flights and find, for instance, for N = 3 and a Levy index {\mu} = 1 that {\alpha} = 1.31 \pm 0.03. Vicious accelerating walkers relate to nocrossing configurations of semiflexible polymer brushes and may prove relevant for a nonMarkovian extension of Dyson's Brownian motion model.EPL (Europhysics Letters) 08/2011; 96(5). · 2.26 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Understanding the effect of motor proteins, such as myosins, on the elasticity of crosslinked actin networks is essential to our understanding of cell mechanics. Both in vivo and in vitro, these active networks have radically different mechanical properties from their equilibrium counterparts, including contractile behavior and higher elastic moduli. Existing theoretical models do not address the relative role of passive and active crosslinkers in controlling the network contractility and stiffening. We construct a one dimensional lattice model with minimal ingredients, that is, rigid polar filaments, springlike passive crosslinks and active crosslinks with on/ off dynamics implemented through nonequilibrium Monte Carlo solution of the corresponding master equations. We find, consistent with experiments, that the network needs to be percolated through the passive crosslinks to be mechanically stable. Contractile behavior is observed for all concentrations of active crosslinks. We study the mechanical properties of the gel in the phase space of motor processivity, crosslink stiffness, and concentration of active crosslinks.03/2011;  [Show abstract] [Hide abstract]
ABSTRACT: In vitro experiments of growing dendritic actin networks demonstrate reversible stresssoftening at high loads, above some critical load. The transition to the stresssoftening regime has been attributed to the elastic buckling of individual actin filaments. To estimate the critical load above which softening should occur, we extend the elastic theory of buckling of individual filaments embedded in a network to include the buckling of branched filaments, a signature trait of growing dendritic actin networks. Under certain assumptions, there will be approximately a sevenfold increase in the classical critical bucking load, when compared to the unbranched filament, which is entirely due to the presence of a branch. Moreover, we go beyond the classical buckling regime to investigate the effect of entropic fluctuations. The result of compressing the filament in this case leads to an increase in these fluctuations and eventually the harmonic approximation breaks down signifying the onset of the buckling transition. We compute corrections to the classical critical buckling load near this breakdown.03/2011;  [Show abstract] [Hide abstract]
ABSTRACT: Actin cytoskeletal protrusions in crawling cells, or lamellipodia, exhibit various morphological properties such as two characteristic peaks in the distribution of filament orientation with respect to the leading edge. To understand these properties, using the dendritic nucleation model as a basis for cytoskeletal restructuring, a kineticpopulation model with orientationaldependent branching (birth) and capping (death) is constructed and analyzed. Optimizing for growth yields a relation between the branch angle and filament orientation that explains the two characteristic peaks. The model also exhibits a subdominant population that allows for more accurate modeling of recent measurements of filamentous actin density along the leading edge of lamellipodia in keratocytes. Finally, we explore the relationship between orientational and spatial organization of filamentous actin in lamellipodia and address recent observations of a prevalence of overlapping filaments to branched filamentsa finding that is claimed to be in contradiction with the dendritic nucleation model.Journal of Mathematical Biology 12/2010; 63(4):73555. · 2.37 Impact Factor  [Show abstract] [Hide abstract]
ABSTRACT: Filopodia are bundles of actin filaments that extend out ahead of the leading edge of a crawling cell to probe its upcoming environment. In vitro experiments (Vignjevic et al. in J Cell Biol 160:951962, 2003) have determined the minimal ingredients required for the formation of filopodia from the dendriticlike morphology of the leading edge. We model these experiments using kinetic aggregation equations for the density of growing bundle tips. In mean field, we determine the bundle size distribution to be broad for bundle sizes smaller than a characteristic bundle size above which the distribution decays exponentially. Twodimensional simulations incorporating both bundling and crosslinking measure a bundle size distribution that agrees qualitatively with mean field. The simulations also demonstrate a nonmonotonicity in the radial extent of the dendritic region as a function of capping protein concentration, as was observed in experiments, due to the interplay between percolation and the ratcheting of growing filaments off a spherical obstacle.Journal of Mathematical Biology 10/2010; 63(2):22961. · 2.37 Impact Factor
Publication Stats
115  Citations  
58.10  Total Impact Points  
Top Journals
Institutions

2003–2014

Syracuse University
 Department of Physics
Syracuse, New York, United States


2012

VU University Amsterdam
 Department of Physics and Astronomy
Amsterdam, North Holland, Netherlands


2010

University of California, Davis
 Department of Mathematics
Davis, CA, United States


2007

University of California, Merced
 School of Natural Sciences
Merced, CA, United States
