arXiv subjects

Michael F. Hagan

Publications and source records attributed to Michael F. Hagan.

At least 73 records · Page 4Linked to original sources

arXiv2015

Orientational order of motile defects in active nematics

The study of liquid crystals at equilibrium has led to fundamental insights into the nature of ordered materials, as well as to practical applications such as display technologies. Active nematics are a fundamentally different class of liquid crystals, driven away from equilibrium by the autonomous motion of their constituent rod-like particles. This internally generated activity powers the continuous creation and annihilation of topological defects, which leads to complex streaming flows whose chaotic dynamics appear to destroy long-range order. Here, we study these dynamics in experimental and computational realizations of active nematics. By tracking thousands of defects over centimetre-scale distances in microtubule-based active nematics, we identify a non-equilibrium phase characterized by system-spanning orientational order of defects. This emergent order persists over hours despite defect lifetimes of only seconds. Similar dynamical structures are observed in coarse-grained simulations, suggesting that defect-ordered phases are a generic feature of active nematics.

cond-mat.soft↗

arXiv2015

Measuring cohesion between macromolecular filaments, one pair at a time: Depletion-induced microtubule bundling

In presence of non-adsorbing polymers, colloidal particles experience ubiquitous attractive interactions induced by depletion forces. Here, we measure the depletion interaction between a pair of microtubule filaments using a method that combines single filament imaging with optical trapping. By quantifying the dependence of filament cohesion on both polymer concentration and solution ionic strength, we demonstrate that the minimal model of depletion, based on the Asakura-Oosawa theory, fails to quantitatively describe the experimental data. By measuring the cohesion strength in two- and three- filament bundles we verify pairwise additivity of depletion interactions for the specific experimental conditions. The described experimental technique can be used to measure pairwise interactions between various biological or synthetic filaments and complements information extracted from bulk osmotic stress experiments.

physics.bio-ph↗

arXiv2014

Hierarchical organization of chiral rafts in colloidal membranes

Liquid-liquid phase separation is ubiquitous in suspensions of nanoparticles, proteins and colloids. With a few notable exceptions, surface-tension-minimizing liquid droplets in bulk suspensions continuously coalesce, increasing in size without bound until achieving macroscale phase separation. In comparison, the phase behavior of colloids, nanoparticles or proteins confined to interfaces, surfaces or membranes is significantly more complex. Inclusions distort the local interface structure leading to interactions that are fundamentally different from the well-studied interactions mediated by isotropic solvents. Here, we investigate liquid-liquid phase separation in monolayer membranes composed of dissimilar chiral colloidal rods. We demonstrate that colloidal rafts are a ubiquitous feature of binary colloidal membranes. We measure the raft free energy landscape by visualizing its assembly kinetics. Subsequently, we quantify repulsive raft-raft interactions and relate them to directly imaged raft-induced membrane distortions, demonstrating that particle chirality plays a key role in this microphase separation. At high densities, rafts assemble into cluster crystals which constantly exchange monomeric rods with the background reservoir to maintain a self-limited size. Lastly, we demonstrate that rafts can form bonds to assemble into higher-order supra-structures. Our work demonstrates that membrane-mediated liquid-liquid phase separation can be fundamentally different from the well-characterized behavior of bulk liquids. It outlines a robust membrane-based pathway for assembly of monodisperse liquid clusters which is complementary to existing methods which take place in bulk suspensions. Finally, it reveals that chiral inclusions in membranes acquire long-ranged repulsive interactions, which might play a role in stabilizing assemblages of finite size.

cond-mat.soft↗

arXiv2014

Virus Assembly on a Membrane is Facilitated by Membrane Microdomains

For many viruses assembly and budding occur simultaneously during virion formation. Understanding the mechanisms underlying this process could promote biomedical efforts to block viral propagation and enable use of capsids in nanomaterials applications. To this end, we have performed molecular dynamics simulations on a coarse-grained model that describes virus assembly on a fluctuating lipid membrane. Our simulations show that the membrane can promote association of adsorbed subunits through dimensional reduction, but also can introduce barriers that inhibit complete assembly. We find several mechanisms, including one not anticipated by equilibrium theories, by which membrane microdomains, such as lipid rafts, can enhance assembly by reducing these barriers. We show how this predicted mechanism can be experimentally tested. Furthermore, the simulations demonstrate that assembly and budding depend crucially on the system dynamics via multiple timescales related to membrane deformation, protein diffusion, association, and adsorption onto the membrane.

q-bio.SC↗

arXiv2014

Dynamics of Self-Propelled Particles Under Strong Confinement

We develop a statistical theory for the dynamics of non-aligning, non-interacting self-propelled particles confined in a convex box in two dimensions. We find that when the size of the box is small compared to the persistence length of a particle's trajectory (strong confinement), the steady-state density is zero in the bulk and proportional to the local curvature on the boundary. Conversely, the theory may be used to construct the box shape that yields any desired density distribution on the boundary. When the curvature variations are small, we also predict the distribution of orientations at the boundary and the exponential decay of pressure as a function of box size recently observed in 3D simulations in a spherical box.

cond-mat.soft↗

arXiv2014

Using Markov State Models to Study Self-Assembly

Markov state models (MSMs) have been demonstrated to be a powerful method for computationally studying intramolecular processes such as protein folding and macromolecular conformational changes. In this article, we present a new approach to construct MSMs that is applicable to modeling a broad class of multi-molecular assembly reactions. Distinct structures formed during assembly are distinguished by their undirected graphs, which are defined by strong subunit interactions. Spatial inhomogeneities of free subunits are accounted for using a recently developed Gaussian-based signature. Simplifications to this state identification are also investigated. The feasibility of this approach is demonstrated on two different coarse-grained models for virus self-assembly. We find good agreement between the dynamics predicted by the MSMs and long, unbiased simulations, and that the MSMs can reduce overall simulation time by orders of magnitude.

physics.bio-ph↗

arXiv2013

Structure and Dynamics of a Phase-Separating Active Colloidal Fluid

We examine a minimal model for an active colloidal fluid in the form of self-propelled Brownian hard spheres that interact purely through excluded volume. Despite the absence of an aligning interaction, this system shows the signature behaviors of an active fluid, including anomalous number fluctuations and phase separation behavior. Using simulations and analytic modeling, we quantify the phase diagram and separation kinetics. The dense phase is a unique material that we call an active hexatic, which exhibits the structural signatures of a crystalline solid near the crystal-hexatic transition point, but the rheological and transport properties associated with a viscoelastic fluid.

cond-mat.soft↗

arXiv2013

Reentrant Phase Behavior in Active Colloids with Attraction

Motivated by recent experiments, we study a system of self-propelled colloids that experience short-range attractive interactions and are confined to a surface. Using simulations we find that the phase behavior for such a system is reentrant as a function of activity: phase-separated states exist in both the low- and high-activity regimes, with a homogeneous active fluid in between. To understand the physical origins of reentrance, we develop a kinetic model for the system's steady-state dynamics whose solution captures the main features of the phase behavior. We also describe the varied kinetics of phase separation, which range from the familiar nucleation and growth of clusters to the complex coarsening of active particle gels.

cond-mat.soft↗

arXiv2013

Viral genome structures are optimal for capsid assembly

Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contrast to recent theoretical models, we find that capsids spontaneously `overcharge'; i.e., the negative charge of the NA exceeds the positive charge on capsid. When applied to specific viruses, the optimal NA lengths closely correspond to the natural genome lengths. Calculations based on linear polyelectrolytes rather than base-paired NAs underpredict the optimal length, demonstrating the importance of NA structure to capsid assembly. These results suggest that electrostatics, excluded volume, and NA tertiary structure are sufficient to predict assembly thermodynamics and that the ability of viruses to selectively encapsidate their genomic NAs can be explained, at least in part, on a thermodynamic basis.

q-bio.BM↗

arXiv2013

Modeling Viral Capsid Assembly

I present a review of the theoretical and computational methodologies that have been used to model the assembly of viral capsids. I discuss the capabilities and limitations of approaches ranging from equilibrium continuum theories to molecular dynamics simulations, and I give an overview of some of the important conclusions about virus assembly that have resulted from these modeling efforts. Topics include the assembly of empty viral shells, assembly around single-stranded nucleic acids to form viral particles, and assembly around synthetic polymers or charged nanoparticles for nanotechnology or biomedical applications. I present some examples in which modeling efforts have promoted experimental breakthroughs, as well as directions in which the connection between modeling and experiment can be strengthened.

q-bio.BM↗

arXiv2012

Flagellar dynamics of a connected chain of active, Brownian particles

Eukaryotic flagella are active structures with a complex architecture of microtubules, motor proteins and elastic links. They are capable of whiplike motions driven by motors sliding along filaments that are themselves constrained at an end. Here, we show that active, self-propelled particles that are connected together to form a single chain that is anchored at one end can produce the graceful beating motions of flagella. We use a combination of numerical simulations, scaling analysis and mean field continuum elastic theory to demarcate the phase diagram for this type of oscillatory motion as a function of the filament length, passive elasticity, propulsion force and longitudinal persistence of propulsion directions. Depending on the nature of the anchoring, we show that filament either undergoes flagella-like beating or assumes a steadily rotating coiled conformation. Our system is simpler than its biological inspiration, and thus could be experimentally realized using a variety of self-propelled particles.

cond-mat.soft↗

arXiv2012

Diffusion-limited rates on low-dimensional manifolds with extreme aspect ratios

We consider a single-species diffusion-limited annihilation reaction with reactants confined to a two-dimensional surface with one arbitrarily large dimension and the other comparable in size to interparticle distances. This situation could describe reactants which undergo both longitudinal and transverse diffusion on long filamentous molecules (such as microtubules), or molecules that undergo truly one-dimensional translational diffusion (e.g. a transcription factor on DNA) but simultaneously exhibit diffusive behavior in a second dimension corresponding to a rotational or conformational degree of freedom. We combine simple analytical arguments and Monte Carlo simulations to show that the reaction rate law exhibits a crossover from one-dimensional to two-dimensional diffusion as a function of particle concentration and the size of the smaller dimension. In the case of a reversible binding reaction, the diffusion-limited reaction rate is given by the Smoluchowski expression, but the crossover is revealed in the statistics of particle collision histories. The results can also be applied to a particle-antiparticle annihilation reaction.

q-bio.BM↗

arXiv2012

Simulations of HIV capsid protein dimerization reveal the effect of chemistry and topography on the mechanism of hydrophobic protein association

Recent work has shown that the hydrophobic protein surfaces in aqueous solution sit near a drying transition. The tendency for these surfaces to expel water from their vicinity leads to self assembly of macromolecular complexes. In this article we show with a realistic model for a biologically pertinent system how this phenomenon appears at the molecular level. We focus on the association of the C-terminal domain (CA-C) of the human immunodeficiency virus (HIV) capsid protein. By combining all-atom simulations with specialized sampling techniques we measure the water density distribution during the approach of two CA-C proteins as a function of separation and amino acid sequence in the interfacial region. The simulations demonstrate that CA-C protein-protein interactions sit at the edge of a dewetting transition and that this mesoscopic manifestation of the underlying liquid-vapor phase transition can be readily manipulated by biology or protein engineering to significantly affect association behavior. While the wild type protein remains wet until contact, we identify a set of in silico mutations, in which three hydrophilic amino acids are replaced with nonpolar residues, that leads to dewetting prior to association. The existence of dewetting depends on the size and relative locations of substituted residues separated by nm length scales, indicating long range cooperativity and a sensitivity to surface topography. These observations identify important details which are missing from descriptions of protein association based on buried hydrophobic surface area.

physics.bio-ph↗

arXiv2012

Mechanisms of budding of nanoscale particles through lipid bilayers

We examine the budding of a nanoscale particle through a lipid bilayer using molecular dynamics simulations, free energy calculations, and an elastic theory, with the aim of determining the extent to which equilibrium elasticity theory can describe the factors that control the mechanism and efficiency of budding. The particle is a smooth sphere which experiences attractive interactions to the lipid head groups. Depending on the parameters, we observe four classes of dynamical trajectories: particle adhesion to the membrane, stalled partially wrapped states, budding followed by scission, and membrane rupture. In most regions of parameter space we find that the elastic theory agrees nearly quantitatively with the simulated phase behavior as a function of adhesion strength, membrane bending rigidity, and particle radius. However, at parameter values near the transition between particle adhesion and budding, we observe long-lived partially wrapped states which are not captured by existing elastic theories. These states could constrain the accessible system parameters for those enveloped viruses or drug delivery vehicles which rely on exo- or endocytosis for membrane transport.

q-bio.SC↗

arXiv2011

Dynamical Self-regulation in Self-propelled Particle Flows

We study a continuum model of overdamped self-propelled particles with an aligning interaction in two dimensions. By combining analytical and numerical work, we map out the phase diagram for generic parameters. We find that the system self-organizes into two robust structures in different regions of parameter space: solitary waves of ordered swarms moving through a low density disordered background, and stationary asters. The self-regulating nature of the flow yields phase separation, ubiquitous in this class of systems, and controls the formation of solitary waves. Self-propulsion and the associated active convection play a crucial role in aster formation. A new result of our work is a phase diagram that displays these different regimes in a unified manner.

physics.bio-ph↗

arXiv2011

Spontaneous Segregation of Self-Propelled Particles with Different Motilities

We study mixtures of self-propelled and passive rod-like particles in two dimensions using Brownian dynamics simulations. The simulations demonstrate that the two species spontaneously segregate to generate a rich array of dynamical domain structures whose properties depend on the propulsion velocity, density, and composition. In addition to presenting phase diagrams as a function of the system parameters, we investigate the mechanisms driving segregation. We show that the difference in collision frequencies between self-propelled and passive rods provides a driving force for segregation, which is amplified by the tendency of the self-propelled rods to swarm or cluster. Finally, both self-propelled and passive rods exhibit giant number fluctuations for sufficient propulsion velocities.

cond-mat.soft↗

arXiv2011

Sitting at the edge: How biomolecules use hydrophobicity to tune their interactions and function

Water near hydrophobic surfaces is like that at a liquid-vapor interface, where fluctuations in water density are substantially enhanced compared to that in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Consequently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance towards or away from the wet state, and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not.

cond-mat.soft↗

arXiv2011

Theoretical calculation of the phase behavior of colloidal membranes

We formulate a density functional theory that describes the phase behavior of hard rods and depleting polymers, as realized in recent experiments on suspensions of \emph{fd} virus and non-adsorbing polymer. The theory predicts the relative stability of nematic droplets, stacked smectic columns, and a recently discovered phase of isolated monolayers of rods, or colloidal membranes. We find that a minimum rod aspect ratio is required for stability of colloidal membranes and that collective protrusion undulations are the dominant effect that stabilizes this phase. The theoretical predictions are shown to be qualitatively consistent with experimental and computational results.

cond-mat.soft↗