Mechanochemical Crosstalk Produces Cell-Intrinsic Patterning of the Cortex to Orient the Mitotic Spindle.

Proliferating animal cells are able to orient their mitotic spindles along their interphase cell axis, setting up the axis of cell division, despite rounding up as they enter mitosis. This has previously been attributed to molecular memory and, more specifically, to the maintenance of adhesions and retraction fibers in mitosis [1-6], which are thought to act as local cues that pattern cortical Gαi, LGN, and nuclear mitotic apparatus protein (NuMA) [3, 7-18]. This cortical machinery then recruits and activates Dynein motors, which pull on astral microtubules to position the mitotic spindle.

Bond breaking dynamics in semiflexible networks under load.

We examine the bond-breaking dynamics of transiently cross-linked semiflexible networks using a single filament model in which that filament is peeled from an array of cross-linkers. We examine the effect of quenched disorder in the placement of the linkers along the filament and the effect of stochastic bond-breaking (assuming Bell model unbinding kinetics) on the dynamics of filament cross-linker dissociation and the statistics of ripping events. We find that bond forces decay exponentially away from the point of loading and that bond breaking proceeds sequentially down the linker array from the point of loading in a series of stochastic ripping events.

Microemulsions, modulated phases and macroscopic phase separation: a unified picture of rafts.

We consider two mechanisms that can lead to an inhomogeneous distribution of components in a multicomponent lipid bilayer: macroscopic phase separation and the formation of modulated phases. A simple model that encompasses both mechanisms displays a phase diagram that also includes a structured fluid, a microemulsion. Identifying rafts with the inhomogeneities of this structured fluid, we see how rafts are related to the occurrence of macroscopic phase separation or the formation of modulated phases in other systems, and focus our attention on specific differences between them.

Phase-locked spiking of inner ear hair cells and the driven noisy Adler equation.

The inner ear constitutes a remarkably sensitive mechanical detector. This detection occurs in a noisy and highly viscous environment, as the sensory cells-the hair cells-are immersed in a fluid-filled compartment and operate at room or higher temperatures. We model the active motility of hair cell bundles of the vestibular system with the Adler equation, which describes the phase degree of freedom of bundle motion.

Macroscopic phase separation, modulated phases, and microemulsions: a unified picture of rafts.

We simulate a simple phenomenological model describing phase behavior in a multicomponent membrane, a model capable of producing macroscopic phase separation, modulated phases, and microemulsions, all of which have been discussed in terms of raft phenomena. We show that one effect of thermal fluctuations on the mean-field phase diagram is that it permits a direct transition between either one of the coexisting liquid phases to a microemulsion. This implies that one system exhibiting phase separation can be related to a similar system exhibiting the heterogeneities characteristic of a microemulsion.

Seeing the Forest in Lieu of the Trees: Continuum Simulations of Cell Membranes at Large Length Scales.

Biological membranes exhibit long-range spatial structure in both chemical composition and geometric shape, which gives rise to remarkable physical phenomena and important biological functions. Continuum models that describe these effects play an important role in our understanding of membrane biophysics at large length scales. We review the mathematical framework used to describe both composition and shape degrees of freedom, and present best practices to implement such models in a computer simulation.

Model of a raft in both leaves of an asymmetric lipid bilayer.

We present a theory of inhomogeneities in the plasma membrane, or rafts, that can exist in both leaves of the plasma membrane. We note that although neither of the major phospholipid components of the outer leaf, sphingomyelin (SM) nor phosphatidylcholine (PC), evinces a tendency to form phases characterized by nonzero curvature, one of the major components of the inner leaf, phosphatidylethanolamine (PE), displays a strong tendency to do so whereas the other, phosphatidylserine (PS), does not. Therefore, we posit that the concentration difference of PS and PE couples to height fluctuations of the plasma membrane bilayer.

Patterning of polar active filaments on a tense cylindrical membrane.

We study the dynamics and patterning of polar contractile filaments on the surface of a cylindrical cell using active hydrodynamic equations that incorporate couplings between curvature and filament orientation. Cables and rings spontaneously emerge as steady state configurations on the cylinder, and can be stationary or moving, helical or tilted segments moving along helical trajectories. We observe phase transitions in the steady state patterns upon changing cell diameter or motor-driven activity and make several testable predictions.

Low frequency entrainment of oscillatory bursts in hair cells.

Sensitivity of mechanical detection by the inner ear is dependent upon a highly nonlinear response to the applied stimulus. Here we show that a system of differential equations that support a subcritical Hopf bifurcation, with a feedback mechanism that tunes an internal control parameter, captures a wide range of experimental results. The proposed model reproduces the regime in which spontaneous hair bundle oscillations are bistable, with sporadic transitions between the oscillatory and the quiescent state.

Measurement of monolayer viscosity using noncontact microrheology.

Microrheological studies of phospholipid monolayers, bilayers, and other Langmuir monolayer systems are traditionally performed by observing the thermal fluctuations of tracers attached to the membrane or interface. Measurements of this type obtain surface moduli that are orders of magnitude different from those obtained using macroscopic or active techniques. These large discrepancies can result from uncertainties in the tracer's coupling to the monolayer or the local disruption of the monolayer by the tracer.

Phase slips in oscillatory hair bundles.

Hair cells of the inner ear contain an active amplifier that allows them to detect extremely weak signals. As one of the manifestations of an active process, spontaneous oscillations arise in fluid immersed hair bundles of in vitro preparations of selected auditory and vestibular organs. We measure the phase-locking dynamics of oscillatory bundles exposed to low-amplitude sinusoidal signals, a transition that can be described by a saddle-node bifurcation on an invariant circle.

Cylindrical cellular geometry ensures fidelity of division site placement in fission yeast.

Successful cytokinesis requires proper assembly of the contractile actomyosin ring, its stable positioning on the cell surface and proper constriction. Over the years, many of the key molecular components and regulators of the assembly and positioning of the actomyosin ring have been elucidated. Here we show that cell geometry and mechanics play a crucial role in the stable positioning and uniform constriction of the contractile ring.

Theoretical model for cellular shapes driven by protrusive and adhesive forces.

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape.

Curling and local shape changes of red blood cell membranes driven by cytoskeletal reorganization.

Human red blood cells (RBCs) lack the actin-myosin-microtubule cytoskeleton that is responsible for shape changes in other cells. Nevertheless, they can display highly dynamic local deformations in response to external perturbations, such as those that occur during the process of apical alignment preceding merozoite invasion in malaria. Moreover, after lysis in divalent cation-free media, the isolated membranes of ruptured ghosts show spontaneous inside-out curling motions at the free edges of the lytic hole, leading to inside-out vesiculation.

Physical model of the dynamic instability in an expanding cell culture.

Collective cell migration is of great significance in many biological processes. The goal of this work is to give a physical model for the dynamics of cell migration during the wound healing response. Experiments demonstrate that an initially uniform cell-culture monolayer expands in a nonuniform manner, developing fingerlike shapes.

Physical model of contractile ring initiation in dividing cells.

We present a physical mechanism to describe initiation of the contractile ring during cell division. The model couples the membrane curvature with the contractile forces produced by protein clusters attached to the membrane. These protein clusters are mobile on the membrane and possess either an isotropic or an anisotropic spontaneous curvature.