Zvonimir Dogic

Spontaneous motion in hierarchically assembled active matter

With remarkable precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometre-sized molecular motors to carry out mechanical tasks at much larger length scales, such as cell motility, division and replication. Besides their biological importance, such inherently non-equilibrium processes suggest approaches for developing biomimetic active materials from microscopic components that consume energy to generate continuous motion. Being actively driven, these materials are not constrained by the laws of equilibrium statistical mechanics and can thus exhibit sought-after properties such as autonomous motility, internally generated flows and self-organized beating. Here, starting from extensile microtubule bundles, we hierarchically assemble far-from-equilibrium analogues of conventional polymer gels, liquid crystals and emulsions. At high enough concentration, the microtubules form a percolating active network characterized by internally driven chaotic flows, hydrodynamic instabilities, enhanced transport and fluid mixing. When confined to emulsion droplets, three-dimensional networks spontaneously adsorb onto the droplet surfaces to produce highly active two-dimensional nematic liquid crystals whose streaming flows are controlled by internally generated fractures and self-healing, as well as unbinding and annihilation of oppositely charged disclination defects. The resulting active emulsions exhibit unexpected properties, such as autonomous motility, which are not observed in their passive analogues. Taken together, these observations exemplify how assemblages of animate microscopic objects exhibit collective biomimetic properties that are very different from those found in materials assembled from inanimate building blocks, challenging us to develop a theoretical framework that would allow for a systematic engineering of their far-from-equilibrium material properties.

An active biopolymer network controlled by molecular motors

We describe an active polymer network in which processive molecular motors control network elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted by bipolar filaments of muscle myosin II. The myosin motors stiffen the network by more than two orders of magnitude by pulling on actin filaments anchored in the network by FLNa cross-links, thereby generating internal stress. The stiffening response closely mimics the effects of external stress applied by mechanical shear. Both internal and external stresses can drive the network into a highly nonlinear, stiffened regime. The active stress reaches values that are equivalent to an external stress of 14 Pa, consistent with a 1-pN force per myosin head. This active network mimics many mechanical properties of cells and suggests that adherent cells exert mechanical control by operating in a nonlinear regime where cell stiffness is sensitive to changes in motor activity. This design principle may be applicable to engineering novel biologically inspired, active materials that adjust their own stiffness by internal catalytic control.

A quantitative analysis of contractility in active cytoskeletal protein networks

Cells actively produce contractile forces for a variety of processes including cytokinesis and motility. Contractility is known to rely on myosin II motors which convert chemical energy from ATP hydrolysis into forces on actin filaments. However, the basic physical principles of cell contractility remain poorly understood. We reconstitute contractility in a simplified model system of purified F-actin, muscle myosin II motors, and alpha-actinin cross-linkers. We show that contractility occurs above a threshold motor concentration and within a window of cross-linker concentrations. We also quantify the pore size of the bundled networks and find contractility to occur at a critical distance between the bundles. We propose a simple mechanism of contraction based on myosin filaments pulling neighboring bundles together into an aggregated structure. Observations of this reconstituted system in both bulk and low-dimensional geometries show that the contracting gels pull on and deform their surface with a contractile force of approximately 1 microN, or approximately 100 pN per F-actin bundle. Cytoplasmic extracts contracting in identical environments show a similar behavior and dependence on myosin as the reconstituted system. Our results suggest that cellular contractility can be sensitively regulated by tuning the (local) activity of molecular motors and the cross-linker density and binding affinity.

Topology and dynamics of active nematic vesicles

Liquid crystals on a deformable substrate The orientation of the molecules in a liquid crystalline material will change in response to either changes in the substrate or an external field. This is the basis for liquid crystalline devices. Vesicles, which are fluid pockets surrounded by lipid bilayers, will change size or shape in response to solvent conditions or pressure. Keber et al. report on the rich interactions between nematic liquid crystals placed on the surface of a vesicle. Changes to the vesicle size, for example, can “tune” the liquid crystal molecules. But conversely, the shape of the vesicles can also change in response to the activity of the nematic molecules. Science, this issue p. 1135 Dynamical shape-changing materials result from merging active liquid crystals with soft deformable vesicles. Engineering synthetic materials that mimic the remarkable complexity of living organisms is a fundamental challenge in science and technology. We studied the spatiotemporal patterns that emerge when an active nematic film of microtubules and molecular motors is encapsulated within a shape-changing lipid vesicle. Unlike in equilibrium systems, where defects are largely static structures, in active nematics defects move spontaneously and can be described as self-propelled particles. The combination of activity, topological constraints, and vesicle deformability produces a myriad of dynamical states. We highlight two dynamical modes: a tunable periodic state that oscillates between two defect configurations, and shape-changing vesicles with streaming filopodia-like protrusions. These results demonstrate how biomimetic materials can be obtained when topological constraints are used to control the non-equilibrium dynamics of active matter.

Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1

The microtubule regulator APC is now shown to also regulate actin filament dynamics through its C-terminal “Basic” domain.

Cilia-Like Beating of Active Microtubule Bundles

In vitro–assembled microtubule bundles exhibit oscillatory beating patterns and organize into metachronal waves. The mechanism that drives the regular beating of individual cilia and flagella, as well as dense ciliary fields, remains unclear. We describe a minimal model system, composed of microtubules and molecular motors, which self-assemble into active bundles exhibiting beating patterns reminiscent of those found in eukaryotic cilia and flagella. These observations suggest that hundreds of molecular motors, acting within an elastic microtubule bundle, spontaneously synchronize their activity to generate large-scale oscillations. Furthermore, we also demonstrate that densely packed, actively bending bundles spontaneously synchronize their beating patterns to produce collective behavior similar to metachronal waves observed in ciliary fields. The simple in vitro system described here could provide insights into beating of isolated eukaryotic cilia and flagella, as well as their synchronization in dense ciliary fields.

Reconfigurable self-assembly through chiral control of interfacial tension

From determining the optical properties of simple molecular crystals to establishing the preferred handedness in highly complex vertebrates, molecular chirality profoundly influences the structural, mechanical and optical properties of both synthetic and biological matter on macroscopic length scales. In soft materials such as amphiphilic lipids and liquid crystals, the competition between local chiral interactions and global constraints imposed by the geometry of the self-assembled structures leads to frustration and the assembly of unique materials. An example of particular interest is smectic liquid crystals, where the two-dimensional layered geometry cannot support twist and chirality is consequently expelled to the edges in a manner analogous to the expulsion of a magnetic field from superconductors. Here we demonstrate a consequence of this geometric frustration that leads to a new design principle for the assembly of chiral molecules. Using a model system of colloidal membranes, we show that molecular chirality can control the interfacial tension, an important property of multi-component mixtures. This suggests an analogy between chiral twist, which is expelled to the edges of two-dimensional membranes, and amphiphilic surfactants, which are expelled to oil–water interfaces. As with surfactants, chiral control of interfacial tension drives the formation of many polymorphic assemblages such as twisted ribbons with linear and circular topologies, starfish membranes, and double and triple helices. Tuning molecular chirality in situ allows dynamical control of line tension, which powers polymorphic transitions between various chiral structures. These findings outline a general strategy for the assembly of reconfigurable chiral materials that can easily be moved, stretched, attached to one another and transformed between multiple conformational states, thus allowing precise assembly and nanosculpting of highly dynamical and designable materials with complex topologies.

Development of model colloidal liquid crystals and the kinetics of the isotropic–smectic transition

We have prepared a homologous series of filamentous viruses with varying contour length using molecular cloning techniques. These viruses are monodisperse enough to form a stable smectic phase. Two systems are studied. The first system consists of viruses to the surfaces of which the polymers are covalently bound. Through studies of the isotropic–cholesteric phase transition we demonstrate that covalently attached polymers alter the effective diameter of the virus. Additionally, we have produced mixtures of viruses whose ratio of effective diameters varies by a factor of five. The second system is composed of mixtures of rod–like viruses and non–absorbing Gaussian polymers. With this system we study the kinetics of the isotropic–smectic phase transition and describe observations of a number of novel metastable structures of unexpected complexity.

Enhanced stability of layered phases in parallel hard spherocylinders due to addition of hard spheres

There is increasing evidence that entropy can induce microphase separation in binary fluid mixtures interacting through hard particle potentials. One such phase consists of alternating two-dimensional liquidlike layers of rods and spheres. We study the transition from a uniform miscible state to this ordered state using computer simulations, and compare results to experiments and theory. We conclude the following: (1) There is stable entropy driven microphase separation in mixtures of parallel rods and spheres. (2) Adding spheres smaller than the rod length decreases the total volume fraction needed for the formation of a layered phase, and therefore small spheres effectively stabilize the layered phase; the opposite is true for large spheres. (3) The degree of this stabilization increases with increasing rod length.

Entropy driven self-assembly of nonamphiphilic colloidal membranes

We demonstrate that homogeneous monodisperse rods in the presence of attractive interactions assemble into equilibrium 2D fluid-like membranes composed of a one-rod length thick monolayer of aligned rods. Unique features of our system allow us to simultaneously investigate properties of these membranes at both continuum and molecular lengthscales. Analysis of thermal fluctuations at continuum lengthscales yields the membranes’ lateral compressibility and bending rigidity and demonstrates that the properties of colloidal membranes are comparable to those of traditional lipid bilayers. Fluctuations at molecular lengthscales, in which single rods protrude from the membrane surface, are directly measured by comparing the positions of individual fluorescently labeled rods within a membrane to that of the membrane’s continuum conformation. As two membranes approach each other in suspension, protrusion fluctuations are suppressed leading to effective repulsive interactions. Motivated by these observations, we propose an entropic mechanism that explains the stability of colloidal membranes and offers a general design principle for the self-assembly of 2D nanostructured materials from rod-like molecules.