Archives: Events

Effects of Cellular Chirality on Competition and Cooperation in Microbial Colonies

Is it better to be left- or right-handed? The answer depends on whether the goal is making a handshake or winning a boxing match. The need for coordination favors the handedness of the majority, but being different could also provide an advantage. The same rules could apply to microbial colonies and cancer tumors. Like humans, cells often have handedness or chirality that reflects the lack of mirror symmetry in their shapes or movement patterns. Moreover, chirality can easily evolve, and a change in chirality is often accompanied by an increase in fitness.

To answer how chirality provides a direct fitness advantage, we developed a minimal reaction-diffusion model of chiral growth in compact microbial colonies. For strains with equal chirality, our model reproduces logarithmic twisting of boundaries between the strains, as observed in the experiments. For strains with different chiralities, our model predicts either the exclusion of the less chiral strain or stable coexistence. Selection for specific chirality is mediated by bulges along the colony edge that appear in regions where the strains with different chirality meet. We developed an analytical framework to study this two-way coupling between selection and colony shape, which is ubiquitous in spatially structured populations, yet remains poorly understood. For chiral strains, the theory of population dynamics is described by the chiral KPZ equation coupled to the Burger’s equation with multiplicative noise. We obtain exact solutions for the key features of this theory including the shape of the bulges and their effect on competition between the strains. Overall, our work suggests that chirality could be an important ecological trait that mediates competition, invasion, and spatial structure in cellular populations.

Active chains in microfluidic channels

The ability to manipulate and organize the collective motion of droplets, cells and filaments in microfluidic channels is relevant to numerous applications in biology and physics, including lab-on-chip applications and the self-assembly of colloids and active materials. Here, I will present a first-principles theory that describes the behavior of passive and active particles and filaments in microfluidic confinement under various external flow conditions. Hydrodynamic interactions between particles lead to interesting and new transitions in the patterns that emerge at the population level, including the development of phonons and density shock waves. These findings could be used to guide the design of novel mechanisms for particle manipulation and control in high-throughput microfluidic devices.

Spontaneous topological charging of tactoids in a living nematic

Living nematic is a realization of an active matter combining a nematic liquid crystal with swimming bacteria. The material exhibits a remarkable tendency towards spatiotemporal self-organization manifested in formation of dynamics textures of self-propelled half-integer topological defects (disclinations). Here we report on the study of such living nematic near normal inclusions, or tactoids, naturally realized in liquid crystals close to the isotropic-nematic (I-N) phase transition. On the basis of the computational analysis, we have established that tactoid’s I-N interface spontaneously acquire negative topological charge which is proportional to the tactoid’s size and depends on the concentration of bacteria. The observed negative charging is attributed to the drastic difference in the mobilities of 1/2 and -1/2 topological defects in active systems. The effect is described in the framework of a kinetic theory for point-like weakly-interacting defects with different mobilities. Our dedicated experiment fully confirmed the theoretical prediction. The results hint into new strategies for control of active matter.

Engineering with kinesin motors

Motor proteins, such as kinesin, can serve as biological components in engineered nanosystems. A proof-of-principle application is a “smart dust” biosensor for the remote detection of biological and chemical agents, which is enabled by the integration of recognition, transport and detection into a submillimeter-sized microfabricated device. The development of this system has revealed a number of challenges in engineering at the nanoscale, particularly in the guiding, activation, and loading of kinesin-powered molecular shuttles. Overcoming these challenges requires the integration of a diverse set of technologies, illustrates the complexity of biophysical mechanisms, and enables the formulation of general principles for nanoscale engineering.

Molecular motors also introduce an interesting new element into self-assembly processes by accelerating transport, reducing unwanted connections, and enabling the formation of non-equilibrium structures. The formation of nanowires and nanospools from microtubules transported by kinesin motors strikingly illustrates these aspects of motor-driven self-assembly.

Our most recent work aimed to create a molecular system that is capable of dynamically assembling and disassembling its building blocks while retaining its functionality, and demonstrates the possibility of self-healing and adaptation. In our system, filaments (microtubules) recruit biomolecular motors (kinesins) to a surface engineered to allow for the reversible binding of the kinesin motors. These recruited motors perform the function of propelling the microtubules along the surface. When the microtubules leave the kinesin motors behind, the kinesin track can either disassemble and release the motors back into solution with the possibility of being reassembled into another track, or recruit other microtubules onto itself, reinforcing the track and thus creating a molecular ‘ant trail’. We show that this allows for more efficient use of the molecular building blocks, and demonstrate that this system is defect tolerant, self-healing, and adaptive.

Molecular Adaptation by Stochastic Pumping

In the absence of input energy, a chemical reaction in a closed system ineluctably relaxes toward an equilibrium state governed by a Boltzmann distribution. The addition of a catalyst to the system provides a way for more rapid equilibration toward this distribution, but the catalyst can never, in and of itself, drive the system away from equilibrium. In the presence of external fluctuations, however, a macromolecular catalyst (e.g., an enzyme) can absorb energy and drive the formation of a steady state between reactant and product that is not determined solely by their relative energies. Due to the ubiquity of non-equilibrium steady states in living systems, the development of a theory for the effects of external fluctuations on chemical systems has been a longstanding focus of non-equilibrium thermodynamics. The theory of stochastic pumping has provided insight into how a non-equilibrium steady-state can be formed and maintained in the presence of dissipation and kinetic asymmetry. This effort has
been greatly enhanced by a confluence of experimental and theoretical work on synthetic molecular machines designed explicitly to harness external energy to drive non-equilibrium transport and self-assembly.

Collective behavior in laboratory populations

Individuals in a population interact in myriad ways, and these interactions can lead to striking collective phenomena. In my laboratory, we use experimentally tractable microcosms to explore how cooperative interactions within a population can lead to tipping points, spatial patterns, and collective decisions. In this talk I will describe ongoing work with micro-organisms and the worm C. elegans.

Broken detailed balance in active biological systems

Measuring and quantifying non-equilibrium dynamics is a major challenge in living systems, due to their many-body nature and the limited number of variables accessible in an experiment. We present a method to identify non-equilibrium dynamics based on broken detailed balance. Using this approach, we study active dynamics in flagella, primary cilia, and cytoskeletal networks. What information concerning the system’s non-equilibrium state can be extracted from detecting broken detailed balance? To answer this question, we develop a general, yet simple model of soft elastic networks with a heterogeneous distribution of activities, representing internal enzymatic force generation. With this model, we determine the scaling behavior of non-equilibrium dynamics, including the entropy production rate. Our results provide insight into how internal driving by enzymatic activity generates non-equilibrium dynamics on different length scales in biological assemblies.

Sedimentation and gravitational instability of Escherichia coli suspension

The successive runs and tumbles of Escherichia coli bacteria provide an active matter suspension of rod-like particles with a large swimming diffusion. As opposed to inactive elongated particles, this diffusion prevents clustering of the particles and hence instability in the gravity field. We measure the time dependent E. coli concentration profile during their sedimentation. After some hours, due to the dioxygen consumption, a motile / non-motile front forms leading to a Rayleigh-Taylor type gravitational instability. Analysing both sedimentation and instability in the framework of active particle suspensions, we can measure the relevant bacteria hydrodynamic characteristics such as its single particle sedimentation velocity and its hindrance volume. Comparing these quantities to the ones of equivalent passive particles (ellipsoid, rod) we tentatively infer the effective shape and size of the bacteria involved in its buoyancy induced advection and diffusion.

Catalytic Enzymes as Active Matter

Pioneering experiments of Ayusman Sen and coworkers challenged the traditional view that enzyme kinetics is only a matter of catalyzing chemical reactions; they show that catalysis enhances enzyme mobility. This is significant to programming spatio-temporal patterns of molecular response to chemical stimulus. This talk will report that the enhanced diffusivity of enzymes is a “run-and-tumble” process analogous to that performed by swimming microorganisms, executed in this situation by molecules that lack the decision-making machinery of microorganisms. One consequence is that enzymes migrate in the direction of lesser reactant concentration when they turn over substrate; they display “anti-chemotaxis.” This run-and-tumble process offers the possible biological function to homogenize product concentration, which could be significant in situations when the reactant concentration varies from spot to spot. Attempts will be made to place these and our related recent findings in the context of larger puzzles in the active matter intellectual community.