Cooperative action of KIF1A Brownian motors with finite dwell time

We study in detail the cooperative action of small groups of KIF1A motors in its monomeric (single-headed) form within an arrangement relevant to vesicle traffic or membrane tube extraction. It has been recently shown that under these circumstances, the presence of a finite dwell time in the motor cycle contributes to remarkably enhance collective force generation [D. Oriola and J. Casademunt, Phys. Rev. Lett. 111, 048103 (2013)]. We analyze this mechanism in detail by means of a two-state noise-driven ratchet model with hard-core repulsive interactions. We obtain staircase-shaped velocity-force curves and show that motors self-organize in clusters with a nontrivial force distribution that conveys a large part of the load to the central motors. Under heavy loads, large clusters adopt a synchronic mode of totally asymmetric steps. We also find a dramatic increase of the collective efficiency with the number of motors. Finally, we complete the study by addressing different interactions that impose spatial constraints such as rigid coupling and raft-induced confinement. Our results reinforce the hypothesis that the specificity of KIF1A to axonal vesicular transport may be deeply related to its high cooperativity.Peer ReviewedPostprint (published version

Cooperative Force Generation of KIF1A Brownian Motors

KIF1A is a kinesin motor protein that can work processively in a monomeric (single-headed) form by using a noise-driven ratchet mechanism. Here, we show that the combination of a passive diffusive state and finite-time kinetics of adenosine triphosphate hydrolysis provides a powerful mechanism of cooperative force generation, implying for instance that ~10 monomeric KIF1As can team up to become ~100 times stronger than a single one. Consequently, we propose that KIF1A could outperform conventional (double-headed) kinesin collectively and thus explain its specificity in axonal trafficking. We elucidate the cooperativity mechanism with a lattice model that includes multiparticle transitions.Peer ReviewedPostprint (published version

Bleb nucleation through membrane pealing

We study the nucleation of blebs, i.e., protrusions arising from a local detachment of the membrane from the cortex of a cell. Based on a simple model of elastic linkers with force-dependent kinetics, we show that bleb nucleation is governed by membrane peeling. By this mechanism, the growth or shrinkage of a detached membrane patch is completely determined by the linker kinetics, regardless of the energetic cost of the detachment. We predict the critical nucleation radius for membrane peeling and the corresponding effective energy barrier. These may be typically smaller than those predicted by classical nucleation theory, implying a much faster nucleation. We also perform simulations of a continuum stochastic model of membrane-cortex adhesion to obtain the statistics of bleb nucleation times as a function of the stress on the membrane. The determinant role of membrane peeling changes our understanding of bleb nucleation and opens new directions in the study of blebs

Spontaneous motility of actin lamellar fragments

We show that actin lamellar fragments driven solely by polymerization forces at the bounding membrane are generically motile when the circular symmetry is spontaneously broken, with no need of molecular motors or global polarization. We base our study on a nonlinear analysis of a recently introduced minimal model [Callan-Jones et al Phys. Rev. Lett. 100, 258106 (2008)]. We prove the nonlinear instability of the center of mass and find an exact and simple relation between shape and center-of-mass velocity. A complex subcritical bifurcation scenario into traveling solutions is unfolded, where finite velocities appear through a nonadiabatic mechanism. Examples of traveling solutions and their stability are studied numericall

Cooperative force generation of KIF1A Brownian motors

KIF1A is a kinesin motor protein that can work processively in a monomeric (single-headed) form by using a noise-driven ratchet mechanism. Here, we show that the combination of a passive diffusive state and finite-time kinetics of adenosine triphosphate hydrolysis provides a powerful mechanism of cooperative force generation, implying for instance that ∼ 10 monomeric KIF1As can team up to become ∼ 100 times stronger than a single one. Consequently, we propose that KIF1A could outperform conventional (double-headed) kinesin collectively and thus explain its specificity in axonal trafficking. We elucidate the cooperativity mechanism with a lattice model that includes multiparticle transitions

Kinetic roughening in two-phase fluid flow through a random Hele-Shaw cell

A nonlocal interface equation is derived for two-phase fluid flow, with arbitrary wettability and viscosity contrast, c = ( μ 1 − μ 2 ) / ( μ 1 + μ 2 ) , in a model porous medium defined as a Hele-Shaw cell with random gap b 0 + δ b . Fluctuations of both capillary and viscous pressure are explicitly related to the microscopic quenched disorder, yielding conserved, nonconserved, and power-law correlated noise terms. Two length scales are identified that control the possible scaling regimes and which scale with capillary number Ca as ℓ 1 ∼ b 0 ( c C a ) − 1 / 2 and ℓ 2 ∼ b 0 C a − 1 . Exponents for forced fluid invasion are obtained from numerical simulation and compared with recent experiments

Self-organization and cooperativity of weakly coupled molecular motors under unequal loading

We study the collective dynamics of Brownian motors moving on a one-dimensional track when an external load is applied to the leading motor. Motors are driven by a two-state ratchet mechanism, which is appropriate to single-headed kinesins, and their relative motion is only constrained by their mutual interaction potential (weak coupling). We show that unequal loading enhances cooperativity, leading to the formation of clusters with velocities and efficiencies higher than those predicted by simple superposition. When a weak attraction between motors is present, we find nonmonotonic collective velocity-force curves, hysteretic phenomena, and a dynamic self-regulation mechanism that selects the cluster size for optimal performance

Nonlinear amplitude dynamics in flagellar beating

The physical basis of flagellar and ciliary beating is a major problem in biology which is still far from completely understood. The fundamental cytoskeleton structure of cilia and flagella is the axoneme, a cylindrical array of microtubule doublets connected by passive cross-linkers and dynein motor proteins. The complex interplay of these elements leads to the generation of self-organized bending waves. Although many mathematical models have been proposed to understand this process, few attempts have been made to assess the role of dyneins on the nonlinear nature of the axoneme. Here, we investigate the nonlinear dynamics of flagella by considering an axonemal sliding control mechanism for dynein activity. This approach unveils the nonlinear selection of the oscillation amplitudes, which are typically either missed or prescribed in mathematical models. The explicit set of nonlinear equations are derived and solved numerically. Our analysis reveals the spatio-temporal dynamics of dynein populations and flagellum shape for different regimes of motor activity, medium viscosity and flagellum elasticity. Unstable modes saturate via the coupling of dynein kinetics and flagellum shape without the need of invoking a nonlinear axonemal response. Hence, our work reveals a novel mechanism for the saturation of unstable modes in axonemal beating

Landscape-Inversion Phase Transition in Dipolar Colloids: Tuning the Structure and Dynamics of 2D Crystals

We study the 2D crystalline phases of paramagnetic colloidal particles with dipolar interactions and constrained on a periodic substrate. Combining theory, simulation, and experiments, we demonstrate a new scenario of first-order phase transitions that occurs via a complete inversion of the energy landscape, featuring nonconventional properties that allow for (i) tuning of crystal symmetry, (ii) control of dynamical properties of different crystalline orders via tuning of their relative stability with an external magnetic field, (iii) an equivalent but independent control of the same dynamic properties via temporal modulations of that field, and (iv) nonstandard phase-ordering kinetics involving spontaneous formation of transient metastable domains

Fluidization and active thinning by molecular kinetics in active gels

We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity active thinning of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues