experiments
Latest
4D Chromosome Organization: Combining Polymer Physics, Knot Theory and High Performance Computing
Self-organization is a universal concept spanning numerous disciplines including mathematics, physics and biology. Chromosomes are self-organizing polymers that fold into orderly, hierarchical and yet dynamic structures. In the past decade, advances in experimental biology have provided a means to reveal information about chromosome connectivity, allowing us to directly use this information from experiments to generate 3D models of individual genes, chromosomes and even genomes. In this talk I will present a novel data-driven modeling approach and discuss a number of possibilities that this method holds. I will discuss a detailed study of the time-evolution of X chromosome inactivation, highlighting both global and local properties of chromosomes that result in topology-driven dynamical arrest and present and characterize a novel type of motion we discovered in knots that may have applications to nanoscale materials and machines.
Towards model-based control of active matter: active nematics and oscillator networks
The richness of active matter's spatiotemporal patterns continues to capture our imagination. Shaping these emergent dynamics into pre-determined forms of our choosing is a grand challenge in the field. To complicate matters, multiple dynamical attractors can coexist in such systems, leading to initial condition-dependent dynamics. Consequently, non-trivial spatiotemporal inputs are generally needed to access these states. Optimal control theory provides a general framework for identifying such inputs and represents a promising computational tool for guiding experiments and interacting with various systems in soft active matter and biology. As an exemplar, I first consider an extensile active nematic fluid confined to a disk. In the absence of control, the system produces two topological defects that perpetually circulate. Optimal control identifies a time-varying active stress field that restructures the director field, flipping the system to its other attractor that rotates in the opposite direction. As a second, analogous case, I examine a small network of coupled Belousov-Zhabotinsky chemical oscillators that possesses two dominant attractors, two wave states of opposing chirality. Optimal control similarly achieves the task of attractor switching. I conclude with a few forward-looking remarks on how the same model-based control approach might come to bear on problems in biology.
Mechano-adaptation in a large protein complex
Macromolecular protein complexes perform essential biological functions across life forms. A fundamental, though yet unsolved question in biology is how the function of such complexes is regulated by intracellular or extracellular signals. For instance, we have little understanding of how forces affect multi-protein machines whose function is often mechanical in nature. We address this question by studying the bacterial flagellar motor, a large complex that powers swimming motility in many bacteria. This rotary motor autonomously adapts to changes in mechanical load by adding or removing force-generating ‘stator’ units that power rotation. In the bacterium Escherichia coli, up to 11 units drive the motor at high load while all the units are released at low load. We manipulate motor load using electrorotation, a technique in which a rapidly rotating electric field applies an external torque on the motor. This allows us to change motor load at will and measure the resulting stator dynamics at single-unit resolution. We found that the force generated by the stator units controls their unbinding, forming a feedback loop that leads to autoregulation of the assembly. We complemented our experiments with theoretical models that provide insight into the underlying molecular interactions. Torque-dependent remodeling takes place within seconds, making it a highly responsive control mechanism, one that is mediated by the mechano-chemical tuning of protein interactions.
Metachronal waves in swarms of nematode Turbatrix aceti
There is a recent surge of interest in the behavior of active particles that can at the same time align their direction of movement and synchronize their oscillations, known as swarmalators. While analytical and numerical models of such systems are now abundant, no real-life examples have been shown to date. I will present an experimental investigation of the collective motion of the nematode Turbatrix aceti, which self-propel by body undulation. I will show that under favorable conditions these nematodes can synchronize their body oscillations, forming striking traveling metachronal waves which, similar to the case of beating cilia, produce strong fluid flows. I will demonstrate that the location and strength of this collective state can be controlled through the shape of the confining structure; in our case the contact angle of a droplet. This opens a way for producing controlled work such as on-demand flows or displacement of objects. I will illustrate this by a practical example: showing that the force generated by the collectively moving nematodes is sufficient to change the mode of evaporation of fluid droplets, by counteracting the surface-tension force, which allow us to estimate its strength.
Growing in flows: from evolutionary dynamics to microbial jets
Biological systems can self-organize in complex structures, able to evolve and adapt to widely varying environmental conditions. Despite the importance of fluid flow for transporting and organizing populations, few laboratory systems exist to systematically investigate the impact of advection on their spatial evolutionary dynamics. In this talk, I will discuss how we can address this problem by studying the morphology and genetic spatial structure of microbial colonies growing on the surface of a viscous substrate. When grown on a liquid, I will show that S. cerevisiae (baker’s yeast) can behave like “active matter” and collectively generate a fluid flow many times larger than the unperturbed colony expansion speed, which in turn produces mechanical stresses and fragmentation of the initial colony. Combining laboratory experiments with numerical modeling, I will demonstrate that the coupling between metabolic activity and hydrodynamic flows can produce positive feedbacks and drive preferential growth phenomena leading to the formation of microbial jets. Our work provides rich opportunities to explore the interplay between hydrodynamics, growth and competition within a versatile system.
How polymer-loop-extruding motors shape chromosomes
Chromosomes are extremely long, active polymers that are spatially organized across multiple scales to promote cellular functions, such as gene transcription and genetic inheritance. During each cell cycle, chromosomes are dramatically compacted as cells divide and dynamically reorganized into less compact, spatiotemporally patterned structures after cell division. These activities are facilitated by DNA/chromatin-binding protein motors called SMC complexes. Each of these motors can perform a unique activity known as “loop extrusion,” in which the motor binds the DNA/chromatin polymer, reels in the polymer fiber, and extrudes it as a loop. Using simulations and theory, I show how loop-extruding motors can collectively compact and spatially organize chromosomes in different scenarios. First, I show that loop-extruding complexes can generate sufficient compaction for cell division, provided that loop-extrusion satisfies stringent physical requirements. Second, while loop-extrusion alone does not uniquely spatially pattern the genome, interactions between SMC complexes and protein “boundary elements” can generate patterns that emerge in the genome after cell division. Intriguingly, these “boundary elements” are not necessarily stationary, which can generate a variety of patterns in the neighborhood of transcriptionally active genes. These predictions, along with supporting experiments, show how SMC complexes and other molecular machinery, such as RNA polymerase, can spatially organize the genome. More generally, this work demonstrates both the versatility of the loop extrusion mechanism for chromosome functional organization and how seemingly subtle microscopic effects can emerge in the spatiotemporal structure of nonequilibrium polymers.
Internal structure of honey bee swarms for mechanical stability and division of labor
The western honey bee (Apis mellifera) is a domesticated pollinator famous for living in highly social colonies. In the spring, thousands of worker bees and a queen fly from their hive in search of a new home. They self-assemble into a swarm that hangs from a tree branch for several days. We reconstruct the non-isotropic arrangement of worker bees inside swarms made up of 3000 - 8000 bees using x-ray computed tomography. Some bees are stationary and hang from the attachment board or link their bodies into hanging chains to support the swarm structure. The remaining bees use the chains as pathways to walk around the swarm, potentially to feed the queen or communicate with one another. The top layers of bees bear more weight per bee than the remainder of the swarm, suggesting that bees are optimizing for additional factors besides weight distribution. Despite not having a clear leader, honey bees are able to organize into a swarm that protects the queen and remains stable until scout bees locate a new hive.
Magic numbers in protein phase transitions
Biologists have recently come to appreciate that eukaryotic cells are home to a multiplicity of non-membrane bound compartments, many of which form and dissolve as needed for the cell to function. These dynamical “condensates” enable many central cellular functions – from ribosome assembly, to RNA regulation and storage, to signaling and metabolism. While it is clear that these compartments represent a type of separated phase, what controls their formation, how specific biological components are included or excluded, and how these structures influence physiological and biochemical processes remain largely mysterious. I will discuss recent experiments on phase separated condensates both in vitro and in vivo, and will present theoretical results that highlight a novel “magic number” effect relevant to the formation and control of two-component phase separated condensates.
Mixed active-passive suspensions: from particle entrainment to spontaneous demixing
Understanding the properties of active matter is a challenge which is currently driving a rapid growth in soft- and bio-physics. Some of the most important examples of active matter are at the microscale, and include active colloids and suspensions of microorganisms, both as a simple active fluid (single species) and as mixed suspensions of active and passive elements. In this last class of systems, recent experimental and theoretical work has started to provide a window into new phenomena including activity-induced depletion interactions, phase separation, and the possibility to extract net work from active suspensions. Here I will present our work on a paradigmatic example of mixed active-passive system, where the activity is provided by swimming microalgae. Macro- and micro-scopic experiments reveal that microorganism-colloid interactions are dominated by rare close encounters leading to large displacements through direct entrainment. Simulations and theoretical modelling show that the ensuing particle dynamics can be understood in terms of a simple jump-diffusion process, combining standard diffusion with Poisson-distributed jumps. Entrainment length can be understood within the framework of Taylor dispersion as a competition between advection by the no-slip surface of the cell body and microparticle diffusion. Building on these results, we then ask how external control of the dynamics of the active component (e.g. induced microswimmer anisotropy/inhomogeneity) can be used to alter the transport of passive cargo. As a first step in this direction, we study the behaviour of mixed active-passive systems in confinement. The resulting spatial inhomogeneity in swimmers’ distribution and orientation has a dramatic effect on the spatial distribution of passive particles, with the colloids accumulating either towards the boundaries or towards the bulk of the sample depending on the size of the container. We show that this can be used to induce the system to de-mix spontaneously.
Imposed flow in active liquid crystals
Inspired by ongoing experiments on three dimensional active gels composed of sliding microtubule bundles, we study a few idealized problems in a minimal hydrodynamic model for active liquid crystals. Our aim is to use flow to determine the value of the coefficient of activity in a continuum theory. We consider the case of apolar active particles that form a disordered phase in the absence of flow, and study how activity affects the swimming speed of a prescribed swimmer, as well as the stability of a fluid interface. We also consider flows of active matter in channels or past immersed objects.
Neural network-like collective dynamics in molecules
Neural networks can learn and recognize subtle correlations in high dimensional inputs. However, neural networks are simply many-body systems with strong non-linearities and disordered interactions. Hence, many-body physical systems with similar interactions should be able to show neural network-like behavior. Here we show neural network-like behavior in the nucleation dynamics of promiscuously interacting molecules with multiple stable crystalline phases. Using a combination of theory and experiments, we show how the physics of the system dictates relationships between the difficulty of the pattern recognition task solved, time taken and accuracy. This work shows that high dimensional pattern recognition and learning are not special to software algorithms but can be achieved by the collective dynamics of sufficiently disordered molecular systems.
Motility control in biological microswimmers
It is often assumed that biological swimmers conform faithfully to certain stereotypes assigned to them by physicists and mathematicians, when the reality is in fact much more complicated. In this talk we will use a combination of theory, experiments, and robotics, to understand the physical and evolutionary basis of motility control in a number of distinguished organisms. These organisms differ markedly in terms of their size, shape, and arrangement of locomotor appendages, but are united in their use of cilia - the ultimate shape-shifting organelle - to achieve self-propulsion and navigation.
Adhering, wrapping, and bursting of lipid bilayer membranes: understanding effects of membrane-binding particles and polymers
Proteins and membranes form remarkably complex structures that are key to intracellular compartmentalization, cargo transport, and cell morphology. Despite this wealth of examples in living systems, we still lack design principles for controlling membrane morphology in synthetic systems. With experiments and simulations, we show that even the simple case of spherical or rod-shaped nanoparticles binding to lipid-bilayer membrane vesicles results in a remarkably rich set of morphologies that can be reliably controlled via the particle binding energy. When the binding energy is weak relative to a characteristic membrane-bending energy, vesicles adhere to one another and form a soft solid gel, which is a useful platform for controlled release. With larger binding energy, a transition from partial to complete wrapping of the nanoparticles causes a remarkable vesicle destruction process culminating in rupture, nanoparticle-membrane tubules, and vesicle inversion. We have explored the behavior across a wide range of parameter space. These findings help unify the wide range of effects observed when vesicles or cells are exposed to nanoparticles. They also show how they open the door to a new class of vesicle-based, closed-cell gels that are more than 99% water and can encapsulate and release on demand. I will discuss how triggering membrane remodeling could lead to shape-responsive systems in the future.
Biology is “messy”. So how can we take theory in biology seriously and plot predictions and experiments on the same axes?
Many of us came to biology from physics. There we have been trained on such classic examples as muon g-2, where experimental data and theoretical predictions agree to many significant digits. Now, working in biology, we routinely hear that it is messy, most details matter, and that the best hope for theory in biology is to be semi-qualitative, predict general trends, and to forgo the hope of ever making quantitative predictions with the precision that we are used to in physics. Colloquially, we should be satisfied even if data and models differ so much that plotting them on the same plot makes little sense. However, some of us won’t be satisfied by this. So can we take theory in biology seriously and predict experimental outcomes within (small) error bars? Certainly, we won’t be able to predict everything, but this is never required, even in traditional physics. But we should be able to choose some features of data that are nontrivial and interesting, and focus on them. We also should be able to find different classes of models --- maybe even null models --- that match biology better, and thus allow for a better agreement. It is even possible that large-dimensional datasets of modern high-throughput experiments, and the ensuing “more is different” statistical physics style models will make quantitative, precise theory easier. To explore the role of quantitative theory in biology, in this workshop, eight speakers will address some of the following general questions based on their specific work in different corners of biology: Which features of biological data are predictable? Which types of models are best suited to making quantitative predictions in different fields? Should theorists interested in quantitative predictions focus on different questions, not typically asked by biologists? Do large, multidimensional datasets make theories (and which theories?) more or less likely to succeed? This will be an unapologetically theoretical physics workshop — we won’t focus on a specific subfield of biology, but will explore these questions across the fields, hoping that the underlying theoretical frameworks will help us find the missing connections.
Spontaneous and driven active matter flows
Understanding individual and macroscopic transport properties of motile micro-organisms in complex environments is a timely question, relevant to many ecological, medical and technological situations. At the fundamental level, this question is also receiving a lot of attention as fluids loaded with swimming micro-organisms has become a rich domain of applications and a conceptual playground for the statistical physics of “active matter”. The existence of microscopic sources of energy borne by the motile character of these micro-swimmers is driving self-organization processes at the origin of original emergent phases and unconventional macroscopic properties leading to revisit many standard concepts in the physics of suspensions. In this presentation, I will report on a recent exploration on the question of spontaneous formation of large scale collective motion in relation with the rheological response of active suspensions. I will also present new experiments showing how the motility of bacteria can be controlled such as to extract work macroscopically.
“Cell Surface Topography: The Role of Protein Size at Cell-Cell Interfaces”
Membrane interfaces formed at junctions between cells are often associated with characteristic patterns of membrane protein organization, such as in epithelial tissues and between cells of the immune system. While this organization can be influenced by receptor clustering, lipid domain formation, and cytoskeletal dynamics, this talk will describe how cell surface molecular height can directly contribute to the spatial arrangement of membrane proteins and downstream signaling. Using a new optical method for characterizing molecular height, together with experiments using giant vesicles in vitro systems and live immune cells, we are investigating how cell surface molecular heights can be key contributors to cell-cell communication.
Flow, fluctuate and freeze: Epithelial cell sheets as soft active matter
Epithelial cell sheets form a fundamental role in the developing embryo, and also in adult tissues including the gut and the cornea of the eye. Soft and active matter provides a theoretical and computational framework to understand the mechanics and dynamics of these tissues.I will start by introducing the simplest useful class of models, active brownian particles (ABPs), which incorporate uncoordinated active crawling over a substrate and mechanical interactions. Using this model, I will show how the extended ’swirly’ velocity fluctuations seen in sheets on a substrate can be understood using a simple model that couples linear elasticity with disordered activity. We are able to quantitatively match experiments using in-vitro corneal epithelial cells.Adding a different source of activity, cell division and apoptosis, to such a model leads to a novel 'self-melting' dense fluid state. Finally, I will discuss a direct application of this simple particle-based model to the steady-state spiral flow pattern on the mouse cornea.
Length Scales and Dynamics in Contractile Active Gels
Most materials deform when external stresses are applied. This paradigm is familiar to sculptors who deform clay to produce structures. However, living materials such as cells and embryos are capable of deforming on their own. Contractile active gels of the proteins actin and myosin are one of the main drivers of force generation in biology. Here I will present experiments that characterize the length-scale behavior of active gel contraction, which find evidence for critical behavior. I will then present experiments that characterize the dynamics of active gel contraction, which identify dynamic precursors to contraction.
Swimming in the third domain: archaeal extremophiles
Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to show that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit.
(What) can soft matter physics teach us about biological function?
The “soft, active, and living matter” community has grown tremendously in recent years, conducting exciting research at the interface between soft matter and biological systems. But are all living systems also soft matter systems? Do the ideas of function (or purpose) in biological systems require us to introduce deep new ideas into the framework of soft matter theories? Does the (often) qualitatively different character of data in biological experiments require us to change the types of experiments we conduct and the goals of our theoretical treatments? Eight speakers will anchor the workshop, exploring these questions across a range of biological system scales. Each speaker will deliver a 10-minute talk with another 10 minutes set aside for moderated questions/discussion. We expect the talks to be broad, bold, and provocative, discussing both the nature of the theoretical tools and experimental techniques we have at present and also those we think we will ultimately need to answer deep questions at the interface of soft matter and biology.
Dynamics of microbiota communities during physical perturbation
The consortium of microbes living in and on our bodies is intimately connected with human biology and deeply influenced by physical forces. Despite incredible gains in describing this community, and emerging knowledge of the mechanisms linking it to human health, understanding the basic physical properties and responses of this ecosystem has been comparatively neglected. Most diseases have significant physical effects on the gut; diarrhea alters osmolality, fever and cancer increase temperature, and bowel diseases affect pH. Furthermore, the gut itself is comprised of localized niches that differ significantly in their physical environment, and are inhabited by different commensal microbes. Understanding the impact of common physical factors is necessary for engineering robust microbiota members and communities; however, our knowledge of how they affect the gut ecosystem is poor. We are investigating how changes in osmolality affect the host and the microbial community and lead to mechanical shifts in the cellular environment. Osmotic perturbation is extremely prevalent in humans, caused by the use of laxatives, lactose intolerance, or celiac disease. In our studies we monitored osmotic shock to the microbiota using a comprehensive and novel approach, which combined in vivo experiments to imaging, physical measurements, computational analysis and highly controlled microfluidic experiments. By bridging several disciplines, we developed a mechanistic understanding of the processes involved in osmotic diarrhea, linking single-cell biophysical changes to large-scale community dynamics. Our results indicate that physical perturbations can profoundly and permanently change the competitive and ecological landscape of the gut, and affect the cell wall of bacteria differentially, depending on their mechanical characteristics.
Physics of Behavior: Now that we can track (most) everything, what can we do with the data?
We will organize the workshop around one question: “Now that we can track (most) everything, what can we do with the data?” Given the recent dramatic advances in technology, we now have behavioral data sets with orders of magnitude more accuracy, dimensionality, diversity, and size than we had even a few years ago. That being said, there is still little agreement as to what theoretical frameworks can inform our understanding of these data sets and suggest new experiments we can perform. We hope that after this workshop we’ll see a variety of new ideas and perhaps gain some inspiration. We have invited eight speakers, each studying different systems, scales, and topics, to provide 10 minute presentations focused on the above question, with another 10 minutes set aside for questions/discussions (moderated by the two of us). Although we naturally expect speakers to include aspects of their own work, we have encouraged all of them to think broadly and provocatively. We are also hoping to organize some breakout sessions after the talks so that we can have some more expanded discussions about topics arising during the meeting.
experiments coverage
22 items
Share your knowledge
Know something about experiments? Help the community by contributing seminars, talks, or research.
Contribute content