November 12, 2020
Toward controlling the kinetics of colloidal self-assembly
Abstract: Proteins fold reliably and quickly, much more quickly than if they explored their configuration space in equilibrium. Can we design colloids to also self-assemble into a target structure on a desired timescale? I will talk about our efforts to understand the kinetics of colloidal self-assembly and how these can be controlled by varying the interactions between the colloids. First I will derive a theory for calculating transition rates between clusters of colloids, which captures the effects of both short-ranged interactions and hydrodynamics that are critical in our experiments. Then I will illustrate the tradeoff between the thermodynamic stability and kinetic accessibility of a target cluster as one varies the interaction parameters. This tradeoff forms a "Pareto front" for self-assembly that we may compute using a genetic algorithm, and I will show how to use the algorithm to find systems where there is almost no tradeoff. Finally, I will touch upon our attempts to find time-varying, nonequilibrium protocols for the interactions that cause a target state to fold as rapidly as desired.
October 8, 2020
Nanoparticle, Segmental & Chain Dynamics in Polymer Nanocomposites
Abstract: Polymer nanocomposites encompass a wide variety of systems comprised of thermoplastics or thermosets and nanoparticles of various shapes and sizes. While a few polymer nanocomposite systems have very well-established applications, the scope of these materials could be expanded further, perhaps even into construction and infrastructure applications that require improved creep performance. This talk will focus on the dynamic properties of polymer nanocomposites wherein there are either neutral or favorable interactions between the nanoparticles and thermoplastics. Using a combination of experimental methods (single particle tracking, ion beam methods, dielectric spectroscopy, modulated DSC, and quasielastic neutron scattering), as well as coarse-grained molecular dynamics simulations, we are developing a comprehensive description of the nanoparticle diffusion and hierarchical polymer dynamics. I will specifically discuss the importance of nanoparticle size and loading, as well as polymer molecular weight and nanoparticle dispersion. Finally, I will present our recent work of the role of nanoparticles on creep properties.
September 24, 2020
Shear Thickening in Active Gels and Frictional Colloids
Abstract: In this talk I will discuss our recent results on the microscopic physical origins of shear thickening in two vastly different materials: colloidal suspensions and active gels. In the first part of my talk, I will introduce a method we have developed that allows us to resolve the spatial distribution of stresses in sheared soft-materials, known as Boundary Stress Microscopy. We have applied this technique suspensions undergoing continuous and discontinuous shear thickening. I will present our results on the existence of clearly defined dynamically localized regions of substantially increased stress that appear intermittently at stresses well above the applied stress. Surprisingly, we find that these spatially distinct and dynamic phases account quantitatively for the observed shear thickening seen in sheared colloidal dispersions (e.g. Oobleck). In the second part of my talk I will discuss our results on the rheology of active matter. Our system is composed of microtubules and kinesin motor proteins that self-assemble to form complexes that propel themselves through the fluid. What results is a dramatic increase in the viscosity of the material with applied shear rate.
August 27, 2020
How to hit HIV where it hurts
Abstract: Infectious disease-causing viruses have plagued humanity since antiquity. Vaccination has often protected against these threats, and saved more lives than any other medical procedure. But, vaccines designed using the empirical paradigms pioneered by Pasteur and Jenner have failed against some pathogens. HIV, a highly mutable virus, is a prominent example. By bringing together theory/computation (rooted in statistical physics and machine learning) with basic and clinical immunology we translated data on HIV protein sequences to knowledge of the HIV fitness landscape – i.e., how the virus’ ability to propagate infection depends on its sequence. Predictions emerging from the fitness landscape were tested positively against in vitro and clinical data. I will discuss how a T cell-based vaccine was designed based on these findings and tested positively in pre-clinical studies in Macaques. I will then describe work aimed toward eliciting antibodies, the other arm of the immune system, that can protect against diverse strains of HIV.
August 20, 2020
Programmed self-assembly with DNA origami: Self-limited oligomerization, cholesteric liquid crystals and icosahedral quasicrystals
Abstract: In this talk, I will provide an overview of the use of oxDNA, a coarse-grained model of DNA at the nucleotide level, to model DNA origami with examples focussing on assemblies of multiple DNA origami. The first example is the 1D-oligomerization of DNA building block that is self-limited due to the non-linear build-up of stress. In the second example, I consider the physical origins of the phase handedness in cholesteric solutions of twisted DNA origami rods. The phase chirality results from the chiral shape fluctuations of the rods which have a preferred handedness that is opposite to the origami's twist. In the third example, I will introduce an approach to design patchy particles so that they can form icosahedral quasicrystals and show how they could be potentially realized with DNA origami. Finally, if time allows, I will show one non-DNA example of programmed self-assembly, namely designing protein complexes to form biocondensates in yeast cells, and the measurement of their 2-component phase diagrams.
August 6, 2020
Self propelling droplets - a biomimetic model system
Abstract: Living things move: ranging from schools of big fish down to single-celled organisms like algae and bacteria. To test and understand the physical principles enabling complex biological locomotion strategies and dynamics, we require well controlled artificial model systems, with minimal complexity while still reproducing a maximum of features. Our system of choice are oil droplets, self propelling in a micellar surfactant solution. In this talk I want to give a flavour of how these can reproduce a wealth of biomimetic phenomena: gait switching, oscillating and helical swimming, interaction via chemical signalling and ordered clustering. All these effects can be explained by fundamental physicochemical models of e.g. hydrodynamic instabilities, molecular kinetics or the topology of nematogenic droplets.
July 30, 2020
Towards operational mastery of biological cells: A physics-based perspective
Abstract: The frontier in operational mastery of biological cells arguably resides at the interface between biology and colloid physics: cellular processes that operate over colloidal length scales, where continuum fluid mechanics and Brownian motion underlie whole-cell scale behavior. It is at this scale that much of cell machinery operates and is where reconstitution and manipulation of cells is most challenging. This operational regime is centered between the two well-studied limits of structural and systems biology: the former focuses on atomistic-scale spatial resolution with little time evolution, and the latter on kinetic models that abstract space away. Colloidal-physics modeling bridges this divide, and may hold a general key to several open questions in biological cell function. I will discuss our physics-based computational model of a biological cell, where biomolecules and their interactions are physically represented, individually and explicitly. With it, we study a model process: translation elongation.
July 2, 2020
Colloidal Assembly & Machine Learning
Abstract: This talk will discuss approaches for optimal feedback control of colloidal assembly on morphing energy landscapes, which are due to colloidal interactions in reconfigurable electric fields. Essential elements of the control approach are developed using machine learning methods. These elements, in the terminology of colloid science (and control science), include: (1) the ability to quantify microstructures and morphology (sense states), (2) the capability to tune colloidal interactions (actuate state changes), (3) information about non-equilibrium microstructure and morphology evolution after tuning colloidal interactions (dynamic model), and (4) determining rules for changing colloidal interactions (control policy) based on current states and the desired state (objective). This talk will describe machine learning tools to develop these elements of a feedback control framework with the objective to assemble circular defect-free crystal states in minimum time. Results will also be presented for scaling to different system sizes and for parallel processes on electrode arrays. Ultimately, implementing these tools together demonstrates an approach to formally control non-equilibrium dynamic processes in colloidal systems, which can be extended to other colloidal interactions and mechanisms as well as different objectives involving anisotropic particle assemblies, non-equilibrium targets, particle navigation, and colloidal machines.
June 18, 2020
Carving non-equilibrium pathways to control self-assembly
Abstract: Active particles are microscopic particles, which can inject energy locally and were made available by recent progress in colloidal science. They are ideal "pump-probes" to explore the emergent properties in soft systems powered from within or control and direct self-assembly at the microscale.
In this talk, I will first show how active particles added to a material can regulate its activity internally and boost the annealing of a colloidal monolayer. It opens a broad range of novel opportunities to thermal treatments, where the properties of matter are not controlled macroscopically but microscopically and in real time by active dopants. Next, I will introduce a new type of self-assembly through a novel approach to devise spinning microrotors that self-assemble and synchronize, from a single type of building block — a colloid that self-propels. Using photo-active particles and light patterns, I will demonstrate the potential of non-equilibrium(phoretic) interactions to program self-assembly and control dynamical colloidal architectures. It shows that, as in living systems, non-equilibrium processes hold the key to the realization of synthetic machines from machines.
Recording of seminar
June 11, 2020
Growing Droplets in Cells and Gels
Abstract: To function effectively, living cells compartmentalize myriad chemical reactions. In the classic view, distinct functional volumes are separated by thin oily-barriers called membranes. Recently, the spontaneous sorting of cellular components into membraneless liquid-like domains has been appreciated as an alternate route to compartmentalization.
I will review the essential physical concepts thought to underlie these biological phenomena, and outline some fundamental questions in soft matter physics that they inspire. Then, I will focus on the coupling of phase separation to elastic stresses in polymer networks. Using a series of experiments spanning living cells and synthetic materials, I will demonstrate that bulk mechanical stresses dramatically impact every stage in the life of a droplet, from nucleation and growth to ripening and dissolution.
These physical phenomena suggest new mechanisms that cells could exploit to regulate phase separation, and open new routes to the assembly of functional materials.
June 4, 2020
Building Order and Adaptiveness in Protein Materials by Chemical Design
Abstract: Proteins represent the most versatile building blocks available to living organisms or the laboratory scientist for constructing functional materials and devices. Underlying this versatility is an immense structural and chemical heterogeneity that renders the programmable self-assembly of proteins a highly challenging design task. To circumvent the challenge of designing extensive non-covalent interfaces for controlling protein self-assembly, we have endeavored to develop strategies that combine elements of inorganic, supramolecular and polymer chemistry. These strategies have led to the construction of 1-, 2- and 3D protein assemblies that couple structural order over many length scales with adaptiveness and stimuli-responsiveness, thus providing an example for the control of bulk-scale properties of biological materials with molecular-scale design.
May 28, 2020
The mechanics of robust tissue folding
Abstract: Tissue folding is a ubiquitous shape change event during development whereby a cell sheet bends into a curved 3D structure. In this talk, I will show that this mechanical process is remarkably robust, and the correct final form is almost always achieved despite internal fluctuations and external perturbations inherent in living systems. While many genetic and molecular strategies that lead to robust development have been established, much less is known about how mechanical patterns and movements are ensured at the population level. I will describe how quantitative imaging, physical modeling and concepts from network science can uncover collective interactions that govern tissue patterning and shape change.
Actin and myosin are two important cytoskeletal proteins involved in the force generation and movement of cells. Both parts of this talk will be about the spontaneous organization of actomyosin networks. First, I will present how out-of-plane curvature can trigger the global alignment of actin fibers and a novel transition from collective to individual cell migration in culture. I will then describe how tissue-scale cytoskeletal patterns can guide tissue folding in the early fruit fly embryo. I will show that actin and myosin organize into a network that spans a large region of the embryo. Redundancy in this supracellular network encodes the tissue’s intrinsic robustness to mechanical and molecular perturbations during folding. Moving forward, deciphering the physical basis of robustness in living systems will inspire new ways to engineer and control biological tissues and bioinspired active materials that can spontaneously fold into predetermined complex 3D shape.
Recording of seminar
May 21, 2020
Collective behavior underlying the mechanobiology of tissues
Abstract: Living cells and tissues are highly mechanically sensitive and active. Mechanical forces and stimuli influence the shape, motility, and functions of cells, modulate the behavior of tissues, and play a key role in diseases as different as osteoarthritis and cancer metastasis. In this talk, I will discuss how collective biophysical properties of tissues emerge from the interplay between different mechanical properties and statistical physics of underlying components. I will use examples of two complementary tissue types to illustrate how the emergent mechanobiology of tissues is facilitated by their heterogeneous and composite nature, and proximity to phase transitions. I will start with mechanical structure-function relationships in articular cartilage (AC), a soft tissue that has very few cells, and its mechanical response is primarily due to its network like extra-cellular matrix. AC is a remarkable tissue: it can support loads exceeding ten times our body weight and bear 60+ years of daily mechanical loading and resist fracture, despite having minimal regenerative capacity. I will discuss the biophysical principles underlying this exceptional mechanical response using the framework of rigidity percolation theory, and compare our predictions with experiments done by our collaborators. Next, I will discuss how differences in cell mechanics, adhesion, and proliferation in a co-culture of breast cancer cells and healthy breast epithelial cells may modulate experimentally observed phase separation and transport properties. Our results may provide insights into the mechanobiology of tissues with cell populations with different physical properties present together, such as during the formation of embryos or the initiation of tumors. By obtaining a mechanistic understanding of the biophysical properties of these two systems, we hope to elucidate principles underlying the robustness and tunability of tissue properties and gain insights into design principles for soft robotics.
Recording of seminar
May 14, 2020
Fascinating flows and emergent mechanics in living animals
Abstract: Organismal behavior results from emergent properties of a large number of physical and biological processes occurring across multiple scales. My overarching research goal is to reveal how biomechanical phenomena at small-scales determine emergent behavior at large-scales in different animal systems. In the first part of my talk, I will show examples of how tissues exhibit liquid-like ‘cellular flows’ while maintaining their integrity, during morphogenesis and development. I will present our surprising discovery of physiological tissue fractures and healing in a simple, early divergent animal - the Trichoplax adhaerens, and demonstrate how fracture mechanics govern extreme plastic shape changes. Next, I will show fascinating bilateral cellular flows during early chick embryo development, and reveal their key role in establishing the embryonic symmetry axis. In the last part of my talk, I will focus on the role of fluid mechanics in marine invertebrates. I will elucidate how a beautiful array of vortex structures around starfish larvae creates a physical tradeoff between feeding and swimming. My research exemplifies the promise of leveraging physics to unearth the general organizing principles underlying fundamental form-function relationships in organismal biology.
May 7, 2020
Cytoskeleton dynamics and function across domains of life
Abstract: Cytoskeletal polymers control the assembly of cellular structures and transport cargo in virtually all known living organisms. Despite their ubiquitous function, these self-assembled powerhouses come in a variety of flavors in terms of sizes, structures, and kinetic properties. In this talk, I will walk through my past and present work on the relationship between the dynamics and cellular function of cytoskeletal systems throughout evolution. Using single-molecule tracking in live cells, I will discuss the mechanisms in which tubulin-like polymers control cell division in bacteria. To further understand how these bacterial filaments evolved to eukaryotic microtubules, my group studies the functions and properties of multiple tubulins in archaea, the last prokaryotic common ancestor of eukaryotes. Interestingly, we see the presence of both eukaryotic-like and bacterial-like tubulin systems, suggesting the first eukaryotes likely comprised prokaryotic traits. We anticipate our results will unveil unprecedented information about self-assembly regimes and the emergency of new biophysical features in cells.>
Recording of seminar
April 23, 2020
Building the cellular skeleton, one molecule at a time
Abstract: Living cells employ self-assembly to build intracellular structures orders of magnitude larger than their individual constituent units. One such example is the actin cytoskeleton, formed from polymerization of actin monomers into linear filaments. Cells use actin polymerization to generate forces required for cell movement and to sense their mechanical environment. Although the key proteins required for actin remodeling have been identified, how they act in concert to produce complex cellular actin dynamics still remains a mystery. The overarching goal of my work is to investigate and reconstitute multicomponent molecular mechanisms underlying physiological actin dynamics. I employ a range of quantitative experimental biophysical approaches such as microfluidics, multispectral single-molecule and single-filament imaging. First, I will show how a dynamic interplay between enhancers (formin) and inhibitors (capping protein) of actin polymerization leads to tunable control of actin assembly. Second, I will present a novel multicomponent mechanism comprising of two actin disassembly factors resulting in over 300‑fold enhancement of actin depolymerization. These results illustrate how the interplay between molecular components and mechanical forces leads to complex cytoskeleton dynamics. My research exemplifies the power of synthetic biological approaches to dissect fundamental molecular mechanisms governing living cells.
April 16, 2020
From Cytoskeletal Assemblies to Living Machines
Abstract: The cytoskeleton has the remarkable ability to self-organize into living machines which underlie diverse cellular processes. These nonequilibrium machines are driven by molecular motor proteins which shape cytoskeletal components into soft active materials. How the properties of these materials emerge from protein-level interactions and energetics is an open question. Here, I’ll present work on the dynamics, mechanics, and energetics of microtubule/motor protein networks. In cell extracts, we’ve found that microtubule networks undergo a spontaneous bulk contraction driven by the motor protein dynein, which can be quantitatively understood using an active fluid model coarse-grained from motor-scale interactions. Additionally, we’ve used picowatt calorimetry to measure the heat dissipated by an active cytoskeletal material composed of purified components and found that the efficiency for generating large-scale flows is remarkably low. Taken together, these results uncover design principles for building active materials and represent a step towards building a thermodynamic understanding of active matter.
April 9, 2020
Nucleation and growth of DNA-programmed crystallization
Abstract: Grafting DNA onto microscopic colloidal particles can `program' them with information that tells them exactly how to self-assemble. Recent advances in our understanding of the specific interactions that emerge due to DNA hybridization have enabled the assembly of a wide variety of crystal structures. However, the dynamic pathways by which these crystals self-assemble are largely unknown. In this talk I will present an experimental study of the nucleation and growth kinetics of colloidal crystallization due to DNA hybridization. Specifically, I will describe a microfluidics-based approach in which we produce hundreds of monodisperse, isolated droplets filled with colloidal particles and then track the formation of crystals within each drop as a function of time. We find that the initial nucleation of crystals from a supersaturated solution involves overcoming a free-energy barrier, whose height depends strongly on temperature and can be described using classical nucleation theory. We also find that once nucleated, colloidal crystals grow at a rate that is limited by the diffusive flux of colloidal particles to the growing crystal surface. Taken together, these two findings quantitatively describe the full dynamic pathway leading from the initial disordered fluid to the final ordered solid. We anticipate that our results will yield new protocols for making higher quality or more complex self-assembled structures by controlling the dynamics of their assembly.
April 2, 2020
Bi-phase emulsion droplets as dynamic fluid optical systems
Abstract: Micro-scale optical components play a critical role in many applications, in particular when these components are capable of dynamically responding to different stimuli with a controlled variation of their optical behavior. Here, we will discuss the potential of easily reconfigurable, micro-scale, bi-phase emulsion droplets as a material platform for dynamic, fluid optical components. Such droplets can act as liquid compound micro-lenses with tunable focal lengths. They can display stunning iridescent structural colors with a rich structure-dependent variation in angular and spectral distribution of reflected coloration. The droplet morphology can be controlled with optical stimuli, chemical perturbations in their environment, and they are also very responsive to minute thermal gradients. Finally, we provide evidence of the droplet’s utility as a fluidic optical element in potential application scenarios.
March 5, 2020
MRSEC Seminar (two presentations)
Spatiotemporal Optimal Control of an Extensile Active Nematic Suspension
Michael Norton, Center for Neural Engineering, Pennsylvania State University
Abstract: Active nematic suspensions are self-driven fluids that exhibit rich spatiotemporal dynamics characterized by director field buckling, defect nucleation/annihilation and chaotic trajectories of those defects. Towards developing experimental methods for controlling these dynamics, we consider an optimal control problem which seeks to find the spatiotemporal pattern of active stress strength required to drive the system towards a desired director field configuration. As an exemplar, we 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 drives the defects to orbit in the opposite direction.
Active Composites of Actin and Kinesin-driven Microtubules
John Berezney, Postdoctoral Fellow, Brandeis University
Abstract: Two major structural proteins, actin and microtubules, form multiple co-existing and interpenetrating filamentous protein networks within the cell cytoplasm. The out-of-equilibrium active reorganization of these structures by molecular motors is necessary for basic physiological processes such as cell division, cell motility, and environmental sensing. While the passive structure and mechanics of such materials have been well documented, the effects of their steady-state out-of-equilibrium reorganization is a site of current research. To demonstrate some of the mechanics governing the active reorganization of these materials, we have built a polymer blend of kinesin-driven microtubule networks which reorganize a passive entangled actin network. We find both the mechanics of the actin network as well as its initial structure can have dramatic effects on the steady-state behavior of the system. To capture the range of behaviors, we build a state diagram which captures the non-equilibrium phenomena we observe.
February 27, 2020
The density and 3D arrangement of actin filaments in the cytoskeleton dictate how myosin Va molecular motors transport their cargo
Abstract: Inside a cell, material must be transported large distances to specific targets. Passive diffusion is too slow and imprecise, so eukaryotic cells employ molecular motors (like myosin Va), which use chemical energy to "walk" along the 3D network of protein filaments (like actin) of the cytoskeleton. Despite a wealth of experimental and theoretical work at the single molecule level, it is unclear how molecular motors work together to navigate their cargoes through the apparent random tangle of the cytoskeleton. I will discuss a series of experiments performed by collaborators at the University of Vermont aimed at unraveling this process, and a mathematical model that makes sense of the experimental results. The central results of this work are that: 1) measurements in 3D can differ fundamentally from similar 2D measurements; 2) the local geometry of an actin intersection dictates if and how long teams of myosin Va motors become stationary; 3) parameters like actin mesh density and cargo size can determine whether motors act as transporters or tethers. This work suggests mechanisms by which cells can regulate intracellular transport.
December 5, 2019
Traveling waves in actin dynamics from reaction-diffusion and non-reaction-diffusion systems
Abstract: Living cells exhibit many forms of spatial-temporal dynamics, including recently-discovered traveling waves. There is evidence that cells use these traveling waves to organize their interiors, improve cell-cell communication, and tune their motility. Some of these traveling waves arise from excitability (positive feedback) and non-local coupling (dynamics that spread spatially on timescales much faster than the timescale of wave motion). My research has studied two traveling waves involving the mechanics of the cytoskeletal protein actin: one that is approximately equivalent to a reaction-diffusion system [Barnhart et al., 2017, Current Biology], and one that is not [Manakova et al., 2016, Biophysical Journal]. For the non-reaction-diffusion wave, we demonstrate conditions for wave travel analogous to ones previously derived for reaction-diffusion waves. We also demonstrate the existence of a "pinned" regime of parameter space absent in the equivalent reaction-diffusion system.
November 21, 2019
Coherent force transmission in disordered particle media, and its relation to macroscopic mechanics
Abstract: Static and flowing granular materials are ubiquitous in nature and industry, but our understanding of their mechanics lags far behind that of fluids. In a densely packed state, granular materials (and other athermal particle aggregates) transmit stress in a manner that belies their microstructural disorder – a subset of the particle contact network is strikingly coherent, wherein contacts are aligned nearly linearly and transmit large forces. The origin of these “force chains” has long been a puzzle. In this talk I will attempt to convey the findings of recent studies in my group, wherein we have used cluster linearity as a network connectivity measure to classify subnetworks of connected contacts. In static granular assemblies and in steady shear, we find a percolation transition at a critical linearity at which the network is sparse, coherent, and contains the force chains. The subnetwork at critical linearity explains some important experimentally observed features of granular materials: the orientation of the clusters strongly reflects the imposed macroscopic stress, and explains distinctive, even anomalous, features of the stress in granular columns. I will end by connecting our findings to some current questions on constitutive models for granular flow, and the statistics of granular packings.
November 14, 2019
Biologically fabricated materials from engineered microbes
Abstract: The intersection between synthetic biology and materials science is an underexplored area with great potential to positively affect our daily lives, with applications ranging from manufacturing to medicine. My group is interested in harnessing the biosynthetic potential of microbes, not only as factories for the production of raw materials, but as fabrication plants that can orchestrate the assembly of complex functional materials. We call this approach “biologically fabricated materials”, a process whose goal is to genetically program microbes to assemble materials from biomolecular building blocks without the need for time consuming and expensive purification protocols or specialized equipment. Accordingly, we have developed Biofilm Integrated Nanofiber Display (BIND), which relies on the biologically directed assembly of biofilm matrix proteins of the curli system in E. coli. We demonstrate that bacterial cells can be programmed to synthesize a range of functional materials with straightforward genetic engineering techniques. The resulting materials are highly customizable and easy to fabricate, and we are investigating their use for practical uses ranging from bioremediation to engineered therapeutic probiotics. Another project in the group focuses on interfacing yeast cells with light harvesting nanoparticles to create inorganic-biohybrids with light-driven enhanced metabolic output.
November 7, 2019
"Hydrodynamics of Active Defects: from chaoe to defect ordering and patterning"
Abstract: Topological defects play a prominent role in the physics of two-dimensional materials. In active nematics, which are orientationally ordered fluids composed of self-driven elongated particles, disclinations can acquire spontaneous self-propulsion and drive self-sustained flows upon proliferation. Here, I present a comprehensive theory of active nematics by recognizing that defects are the relevant excitations in the system. Upon extending the well-known Coulomb gas mapping of equilibrium defects to the active realm, we develop an effective particle like description of interacting active defects. Using this, we demonstrate that activity drives a nonequilibrium defect unbinding transition to active turbulence, which can further transition to a novel defect ordered flock at high activity. Furthermore, within a hydrodynamic approach, we also show that spatially inhomogeneous activity can be used to pattern and segregate defects, demonstrating the versatility and relevance of our framework to control and design transport in active metamaterials and devices.
October 24, 2019
"Biomechanical imaging of cancer cells and tumor development in 3D"
Abstract: Sculpting of structure and function of three-dimensional multicellular tissues depend critically on the spatial and temporal coordination of cellular physical properties. Yet the organizational principles that govern these events, and their disruption in disease, remain poorly understood. Here, I will introduce our recent progress performing biomechanical imaging to quantify cell and extracellular matrix (ECM) mechanics, as well as their mechanical interaction. By integrating confocal microscopy with optical tweezers, we have developed a platform to map in three dimensions the spatial and temporal evolution of positions, motions, and physical characteristics of individual cells throughout a growing mammary cancer organoid model. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, suppression of which delays transition to an invasive phenotype. Together, these findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression. Furthermore, I will introduce our recent progress on experimentally characterizing the local matrix stiffening induced by contraction of individual living cells inside a 3D biopolymer matrix, and will also introduce a method, called Nonlinear Stress Inference Microscopy, with which we can determine the cell-induced local matrix stress from nonlinear microrheology measurements inside various types of extracellular matrix in 3D.
September 26, 2019
“DNA origami: The bridge to the bottom”
Abstract: Conventional top-down nanofabrication, over the last six decades, has enabled almost all the complex electronic, optical and micro-fluidic devices that form the foundation of our society. Parallel efforts, exploring bottom-up self-assembly processes, have also enabled design and synthesis of structures like quantum dots, carbon nanotubes and unique bio-molecules that possess technologically relevant proper- ties unachievable top-down. While both these approaches have independently matured, ongoing efforts to create “hybrid nanostructures” combining both strategies, has been fraught with technical challenges. The main roadblock is the absence of a scalable method to deterministically organize components built bottom-up within top-down nanofabricated structures. In this talk, I will first introduce a directed self-assembly technique that utilizes DNA origami as a molecular adaptor to modularly position, and orient, bottom-up nano-components (like quantum dots, light emitters and proteins) within top-down nanofabricated devices. I will then present experimental results demonstrating the utility of the technique to achieved absolute, arbitrarily scalable, control over the integration of discrete emitters inside optical devices. Finally, I conclude by presenting my vision of how a DNA origami based bridge between top-down and bottom-up nanofabrication can enable a range of highly transformative, and functional, devices. Specifically, I will present data demonstrating arrays of single-photon sources, method for extremely economical nanotexturing as well as a modular molecular interface between biology and solid-state.
“Functional Kirigami Mechanical Metamaterials for Actuators, Muscles, and Grippers”
Abstract: It is far easier to bend an object than it is to stretch it, and so how does one design thin structures capable of stretching and adopting complex shapes? In recent years, scientists have used cuts in thin sheets to provide local regions that can easily deform. Termed kirigami, in reference to the ancient Japanese art of folding and cutting paper, kirigami-based mechanical metamaterials have provided a simple way to to endow a generic material with extraordinary properties. Lattice cuts, in which cuts are oriented perpendicular to the stretching direction, provide a simple way to enhance the stretchability of a thin sheet. We show that certain lattice configurations are more stretchable than others, while certain configurations produce an array of bistable unit cells. The bistability provides a means to tune the stiffness of the structure in situ, while also providing a means for mechanical memory. We demonstrate the how to switch between stable states using magnetic actuation. Lattice cuts on a curved sheets, i.e. kirigami shells, enable additional functionality. The natural curvature of the sheet causes the bistable lattices to curve together and close around an object, which enables the kirigami shells to act as soft robotic grippers. Finally, non-lattice cuts open up a range of actuation possibilities. Coupling these soft rotation modes with stiff lift modes enables us to generate kirigami linear actuators, that exhibit pitch, yaw, roll and lift in response to uniaxial stretching. The underlying buckling mechanism is independent of thickness to a first order approximation, and thus these results translate down to 2D materials such as graphene and MoS2, as we demonstrate with MD simulations.
September 12, 2019
“Practical Questions in Network Synchronization: Control and Optimization”
Abstract: Collective behavior in large ensembles of network-coupled dynamical systems remains an active area of research in the nonlinear dynamics and networks science communities. Applications stem from both natural and man-made systems, e.g., cardiac pacemaker cells, synthetic cell circuits and power grids. Researchers’ efforts have illuminated rich nonlinear phenomena in heterogeneous oscillator systems, including the onset of synchronization, effects of community structure and effects of time delay. However, important practical questions remain, including: (i) How can heterogeneous oscillator networks be optimized for synchronization? and (ii) What is the most efficient protocol for controlling heterogeneous oscillator networks? In this talk I will present a body of work that explores and answers these important questions. Central to this work is the development of several theoretical tools, including the Synchrony Alignment Function, which quantifies the interplay between a complex network structure and the heterogeneous internal dynamics of each oscillator. Using these new developments, I will show how to implement solutions to practically constrained problems and explore the structural and dynamical properties that are critical in controlling and optimizing oscillator networks.
September 5, 2019
“Systems-Level Control of Structural Hierarchy”
Abstract: Structural hierarchy is a powerful design concept where specific geometric motifs are used to influence material structure across multiple size regimes. These complex levels of organization are typically achieved in the laboratory by conceptually breaking a material down into the smallest components that can be manipulated (e.g. individual molecules, macromolecules, or nanoparticles), and manipulating the thermodynamics of chemical bonding between those components to control how they build up into larger length scale patterns. Conversely, complex assemblies in natural systems are commonly achieved through a more holistic approach where assembly behaviors at the molecular, nano, and macroscopic scales are interlinked. This means that not only does structural information contained in molecular building blocks filter upwards to dictate material form at the nano to macroscopic levels, but also that the environment created by the larger length scale features can affect the behavior of individual components. Here, we will discuss two different methods to synthesize materials in a systems-focused approach that mimics nature's ability to general complex structural motifs across a wide range of size regimes. The first uses nanoscale design handles to deliberately control the multivalent assembly of particle-grafted supramolecular binding moieties, where control over both molecular and nanostructure of material building blocks is then used to manipulate the mesoscale structure of the resulting materials. The second uses macroscopic interfaces to dictate the assembly behavior of DNA-grafted nanoparticles, generating superlattice architectures with controlled sizes, shapes, and orientations. Together, these techniques allow for systems-level approaches to materials design, expanding our ability to program hierarchical ordering at the molecular, nano, and macroscale simultaneously.
August 29, 2019
“Environmentally regulated self-assembly of the bacterial flagellar motor”
Abstract: Macromolecular protein complexes perform essential biological functions across life forms. The assembly of such complexes is known to be regulated at the level of gene transcription, but little is known about the factors that control their assembly once the mature protein subunits enter their target space (cytoplasm, membrane, or cell wall). Even less is known about how their assembly is regulated by extracellular signals from the environment. The bacterial flagellar motor is a large macromolecular machine that powers motility in bacteria. The torque-generating stator units of the motor assemble and disassemble in response to changes in external load. We used electrorotation (applying high frequency rotating electric fields) to drive tethered cells forward, which decreases motor load, and measured the resulting stator dynamics. No disassembly occurred while the torque remained high, but all of the stator units were released when the motor was spun forward at high speed. When the electrorotation was turned off, so that the load was again high, stator units were recruited, increasing motor speed in a stepwise fashion. A model in which speed affects the binding rate and torque affects the free energy of bound stator units captures the observed stator assembly and disassembly dynamics, providing a quantitative framework for the environmentally regulated self-assembly of a major macromolecular machine.