From living cells to tissues: opportunities from mesoscale mechanobiology
When individual cells of the same type gradually assemble into a more confluent unit, they form a higher hierarchical structure known as a cellular collective. As physical connections develop among these identical cellular units, a cellular collective advances to a higher supracellular hierarchical level, often referred to as a proto-tissue in order to distinguish it from more complex tissue architectures. The simplest form of proto-tissue is the epithelial cellular monolayer, a key tissue for maintaining the physiological functions of organs and systems in our body and, as such, also playing a significant role in the progression of deadly diseases such as carcinomas. Mesoscale mechanobiology investigates how mechanics at the level of individual cells integrate at a supracellular scale, leading to the emergence of prototissues from assemblies of individual cells. This integration process gives rise to emergence of new functions and behaviours (both biological and mechanical) which are uniquely available at the higher hierarchical level but not at the lower one. In this presentation, I will provide examples from my research on in vitro supracellular systems to illustrate and discuss the opportunities offered by mesoscale mechanobiology for regenerative and clinical purposes.
Abstract: We study collections of self-propelled dipolar particles, which spontaneously form traveling strings at low packing fractions. We compare Brownian dynamics simulations using LAMMPS with an active Rouse model of flexible polymers. The collective speed and translational diffusion of the string decay with its length. By analyzing the local tangent vector correlation function, we find an active stiffness, which is only possible because the system is out of equilibrium. The stiffness which can be estimated from spatially correlated fluctuations, emerges because of the finite relaxation time of the active driving. We compare the theory and simulation to an experiment of electrically driven active dipolar colloids.
Speaker: Yoav Lahini -- School of Physics, Tel Aviv University
Title: Crumpled sheets reveal (some of) the secrets of glassy dynamics: Physical aging via avalanches of localized instabilities.
Abstract: When a thin sheet is crumpled, it undergoes irreversible plastic deformations, resulting in a permanent network of folds and creases. This violent process also changes the sheet’s mechanical properties, endowing it with a range of unusual behaviors. Most prominently, the crumpled sheet fails to reach equilibrium under constant external loading. Instead, it exhibits an ever-slowing logarithmic relaxation, spanning many time scales – from fractions of a second to several weeks. This process, termed physical aging, is characteristic of many nonequilibrium disordered and glassy systems, yet the microscopic processes underlying the dynamic slow-down during aging and the reason for its similar occurrence in different systems remain poorly understood.
Here, we leverage the macroscopic nature of crumpled sheets to reveal the mechanism underlying slow relaxations. Combining experiments and simulations of a minimal mechanical model, we show that during aging the system dwells at a marginally stable state, where it can stay for long but finite times. These quiescent dwell times are interrupted intermittently by local instabilities, which facilitate each other to form scale-free avalanches. We reconstruct the energy landscape and its evolution over time, showing that a slow increase of local energy barriers results in prolonged dwell times between avalanches, generically leading to logarithmic aging.
The emerging picture is of a highly frustrated disordered system with a complex energy landscape, that self-organizes to a state which lies on the edge of stability. I’ll discuss the possible relevance of this picture to other disordered and glassy systems.
Read more here:
Memory from coupled instabilities in unfolded crumpled sheets, PNAS (2022)
Logarithmic aging via instability cascades in disordered systems, Nature Physics (2023)
NON-ABELIAN METAMATERIALS Emergent computing and memory
Title: "Few Experiments on Active Polymer-Like T. Tubifex Worms"
We propose a new 'active particle' system in which the particles are in fact polymer-like: the Tubifex tubifex or 'sludge' worm.
I will discuss few recent experiments that highlight the richness of this active system. In the first experiment, we perform classical rheology experiments on this entangled polymer-like system. We find that the rheology is qualitatively similar to that of usual polymers, but, quantitatively, (i) shear thinning is reduced by activity, (ii) the characteristic shear rate for the onset of shear-thinning is given by the time scale of the activity, and (iii) the low shear viscosity as a function of concentration shows a very different scaling from that of regular polymers. The level of activity can be controlled by changing the temperature but also by adding small amounts of alcohol to make the worms temporarily inactive.
In a second experiment, we disperse the worm in a quasi-2D aquarium and observe their spontaneous aggregation to compact, highly entangled blobs; a process similar to polymer phase separation, and for which we observe power-law growth kinetics. We find that the phase separation of active polymer-like worms does not occur through Ostwald ripening, but through active motion and coalescence of the phase domains. Interestingly, the growth mechanism differs from conventional growth by droplet coalescence: the diffusion constant characterizing the random motion of a worm blob is independent of its size, a phenomenon that can be explained from the fact that the active random motion arises only from the worms at the surface of the blob. This leads to a fundamentally different phase-separation mechanism, that may be unique to active polymers. Finally, in the remaining time, I will briefly show that we can efficiently separate by size and activity these living polymers using hydrodynamic chromatography technics.
Title: Putting a spin on metamaterials: Mechanical incompatibility as magnetic frustration
Extraordinary responses of mechanical metamaterials often stem from incompatibility of their elementary building blocks. Relying on analogies to ferromagnetic and antiferromagnetic interactions, we describe the deformation fields in complex mechanical metamaterials by discrete spin states. We show how spin frustration relates to mechanical incompatibility, and we use this to design, anlyze, and realize comlex mechanical metamaterials with novel functionalities; We employ combinatorial strategies to construct metamaterials that can deform to arbitrary numbers of pre-defined textures. We use topological defects to steer deformations and stresses towards desired parts of the system. We construct topologically non-trivial knots and links in the defect pattern or in the deformation field. We use the degenerate and disordered manifold of mechanically stable states to detect the sequence of operations that a material underwent.
Speaker: Liam Holt (Associate Professor, Institute for Systems Genetics New York University School of Medicine)
Title: Crowding, compression, and condensation.
Abstract: Thousands of biochemical reactions occur simultaneously in the cell. Small molecules are
channeled through metabolic pathways at blistering speed. Giant complexes assemble to
orchestrate transcription and translation. ATP fuels the active transport of organelles along
microtubules, and actin networks drive membrane remodeling and agitate the cytoplasm. All of
this occurs within a crowded cell interior that approaches the physical limits where molecular
jamming and glassy transitions can occur. This extreme physical environment is both essential
for life, and a potential liability. If cells become too dilute, they senesce and die. On the other
hand, mechanical compression increases crowding and eventually stalls growth. Perturbations
to crowding change the balance of reaction rates in the cell. Crowding also drives biomolecular
condensation, which in turn is thought to regulate myriad processes. We propose that
perturbations to the physical properties of the cell interior through metabolic changes and
mechanical compression play an important role in both normal cell biology and disease.
Liam Holt completed his Ph. D. at UCSF in 2009, was a Bowes Fellow at UC Berkeley, and is currently Associate Professor of Biochemistry at New York University. His lab studies how mechanical compression affects cells, and how the physical properties of the cell interior affect biochemistry in both normal biology and disease. He is passionate about outreach and community: he co-founded Science Sketches (www.sciencesketches.org), an online dictionary of science videos partnered with the Explorer’s Guide to Biology (www.explorebiology.org) and MBoC Journal; and Inspire Science (www.inspiresci.org), a symposium about maintaining happiness in a challenging career.
Website: www.liamholtlab.org, www.sciencesketches.org, www.inspiresci.org.
``Liam Holt's lab studies tissue mechanics and the biophysical properties of cells.''
Speaker: Amir Shee (Northwestern University)
Title:Noise-induced quenched disorder in active elastic systems
Abstract: Self-organization is often observed in active systems such as cell colonies, developing tissue, insect swarms, bird flocks, and groups of autonomous robots. In recent years, several minimal models have been introduced to understand the underlying mechanisms that can lead to the emergence of large-scale coherent patterns of motion in such systems for different types of individual dynamics and interactions.
In this work, we consider a dense sheet of self-propelled disks with elastic repulsive forces
that act on their positions and orientations. Each disk can move along its heading direction or rotate about a center of rotation located behind its barycenter. This system displays three phases: polar moving order, standard dynamic disorder, and a novel noise-induced state of quenched disorder, in which the disks are jammed, and orientations fluctuate about fixed random directions.
We explain the mechanism that leads to the quenched state by formulating an approximate analytical description in which the heading fluctuations follow an Ornstein–Uhlenbeck process. Finally, we argue that this state could be observed in a broad range of natural and artificial dense active systems with repulsive interactions.
Speaker 1: Leonardo Passerini (Huber Lab)
Title: Identifying a short lived intermediate of oxygen reduction in a copper enzyme by EPR
Speaker 2: Gert-Jan Kuijntjes (v. Noort Lab)
Title: Single-Molecule Nucleosome Mapping through Nanopore Sequencing
Speaker: Michael M. Lerch is currently an assistant professor at the University of Groningen (the Netherlands), working on self-regulated soft materials and soft robotics (www.lerchlab.com). He holds a PhD in supramolecular and photochemistry based on his work on ‘Donor–Acceptor Stenhouse Adducts’ with Prof. Feringa. During a NWO Rubicon postdoctoral fellowship in the Aizenberg group at Harvard University/WYSS Institute, he developed microstructured liquid crystalline elastomer surfaces with self-regulated motion and feedback-controlled optically active hydrogels.
Title: Operating Soft Matter Through Engineered Feedback
Abstract: Eliciting complex movements in soft matter generally requires extensive external control or complicated material architectures. Both are impractical, particularly at small scales. A promising approach to avoid laborious fabrication or operation is to engineer feedback within the material, so the material deformations become self-regulated.
While self-regulation is abundant in natural systems, it is surprisingly difficult to design for in synthetic systems. In this talk, I will present our recent work on creating opto-chemo-mechanical feedback in liquid crystalline elastomers and hydrogels. We show that using a light-responsive crosslinker and a simple symmetry argument, one can design microstructures that twist and bend on demand and at higher light intensity undergo power-stroke type deformations. Interestingly, such microstructures can form self-organized deformation patterns in arrays, based on the same opto-chemo-mechanical feedback mechanism. Overall, the simplicity of the system offers a new approach to motional complexity in soft matter.
Speaker: Iain Muntz
Title: A Minimal Tissue Model: The Cell as a Physical Object
Abstract: Human tissues are complex systems composed of cells embedded in an extracellular matrix (ECM), a network of polymers which confers mechanical and structural integrity on the tissue. In addition, the ECM provides physical cues to the cells that affect their biological activity. Conversely, cells affect tissue mechanics by a volume exclusion effect combined with biochemical remodelling. The biophysics of the ECM-cell interplay in tissue mechanics is challenging to study because of the huge molecular complexity of the ECM and the reciprocal mechanochemical crosstalk of cells and ECM.
To tackle this challenge, we develop a minimal tissue model to understand how cells affect tissue mechanics through purely physical effects, specifically the volume exclusion interaction. To do this we use poly(acryl amide) based microgels as a proxy for the cell. We show that networks of fibrin, which exhibit compression-softening, instead stiffen under compression when cell-mimetic microgels are embedded in the network. This effect is, at least partially, explained through stretching of the network in between the beads due to the inhomogeneities in the system. However, we observe stronger than expected stiffening effects at short times which we postulate arise from poroelastic effects in the system, where fluid flows through the porous network initially dominate the response. These results are important to understand not only native tissue mechanics, but also as a step to producing tissue engineered constructs with properties more closely resembling those of native tissue.
Speaker 1: Vasilii Akulov (v. Noort Lab)
Speaker 2: Jacco Ton (Orrit Lab)
Speaker 1: Nasrin Asgari (Orrit Lab)
Title: Burst-by-burst analyzes of the rotational diffusion of single gold nanorods
Speaker 2: Robert Smit (Orrit Lab)
Title: Spectroscopy of single molecules on the surface of hexagonal Boron Nitride
Speaker1: ThéoTravers,Orrit Lab
Title:Characterization of the free diffusion of light nanosources using nonlinear microscopy
Speaker2: Georgia Kefala,Schmidt Lab
Title:Interaction forces and cell sorting between two different cell types in hetero-spheroids.
|13:00||Deems Ioratim-Uba (Silke's group)|
|13:15||Amitesh Singh (Martin's group)|
|13:30||Jose (Luca's group)|
|13:45||Julio Melio (Daniela's group)|
|14:45||Solenn Riedel (Daniela's group)|
|15:00||Samadarshi Maity (Alexandre's group)|
|15:15||Dimitris (Luca's group)|
|16:00||Parisa Omidvar (Marc Serra Garcia's group)|
|16:15||Colin Meulblok (Martin's group)|
|16:30||Marine Le Blay (Alexandre's group)|
Speaker: Tannie Liverpool
Title: The mathematics of active matter
Abstract: A flock of birds, a shoal of fish, a swarm of robots, a colony of swimming bacteria; these are examples of systems composed of interacting units that consume energy and collectively generate motion and mechanical forces on their environment. They show a rich variety of collective behaviour, much of which remains mysterious. In recent years we have come to call such systems active matter. Clearly, biology (living systems) provides numerous examples of these active matter systems.
We call them active matter because they share some of the properties of the constituents of what we call matter, i.e. solids, liquids and gases in that they are made of many interacting components. However they have fundamental differences in that many conservation laws that govern the interactions of normal (passive) matter are not obeyed by their active components.
(Equilibrium) statistical mechanics has formed the framework for how we understand the properties of matter. I will argue that ideas developed in statistical mechanics must be augmented by a number of new mathematical structures to describe these systems. Then I will describe some recent theoretical work developing this framework for characterising the behaviour of active matter systems. Finally I will apply it to describe two examples of active systems, active Brownian particles and active nematics.
Speaker: Victor Yashunsky (Ben Gurion University, Be'er Sheva, Israel)
Title: Chiral edge current in chaotic nematic cell monolayers
Abstract: Collective migration of cancer cells in the body is routinely observed close to confining structures such as muscle fibers or blood vessels. In vitro studies re-create such behavior by showing that fibrosarcoma cells collectively migrate at the border of their colony, even though within the monolayer cell flows obey turbulent chaotic dynamics characterized by an irregular array of vortices generated by self-propelled units. Even more surprising is that the edge currents always flow in the same direction—somehow cells collectively distinguish between their left and right near the edge. To understand this situation, we looked deeper at the organization of the cells within the monolayers. Fibrosarcoma cells are elongated and align together, defining a patchwork of well-aligned domains between which orientational singularities (topological defects) position themselves. In the bulk of the monolayer, the position and orientation of these defects randomly change over time. However, close to the boundary, we find that comet-shaped "+½ defects" orient themself with an angle slightly smaller than 90° relative to the boundary, consistently tilting their tails to the right. Because of this left-right symmetry breaking, clockwise vortices are pushed closer to the border and generate the directed edge flow. Modeling the system as a chiral, active, nematic liquid crystal accounts well for our results and demonstrates that cell handedness is a critical ingredient for the emergence of the observed edge flows and not only for their direction.
Title: Non-orientable order and non-commutative response in frustrated metamaterials
Abstract: From atomic crystals to animal flocks, the emergence of order in nature is captured by the concept of spontaneous symmetry breaking. However, this cornerstone of physics is challenged when broken-symmetry phases are frustrated by geometrical constraints. Such frustration dictates the behavior of systems as diverse as spin ices, confined colloidal suspensions, and crumpled paper sheets. These systems typically exhibit strongly degenerated and heterogeneous ground states and hence escape the Ginzburg-Landau paradigm of phase ordering.
Here, combining experiments, simulations and theory we uncover an unanticipated form of topological order in globally frustrated matter: non-orientable order. We demonstrate this concept by designing globally frustrated metamaterials that spontaneously break a discrete Z_2 symmetry. We observe that their equilibria are necessarily heteregeneous and extensively degenerated. We explain our observations by generalising the theory of elasticity to non-orientable order-parameter bundles. We show that non-orientable equilibria are extensively degenerated due to the arbitrary location of topologically protected nodes and lines where the order parameter must vanish. We further show that non-orientable order applies more broadly, to objects that are non-orientable themselves, such as buckled Mobius strips and Klein bottles. Finally, applying time dependent local perturbations to metamaterials enjoying non-orientable order, we engineer topologically protected mechanical memories, we achieve non-commutative responses, and show that they carry an imprint of the braiding of the loads’ trajectories.
Beyond mechanics, we envision non-orientability as a robust design principle for metamaterials that can effectively store information across scales, in fields as diverse as colloidal science, photonics, magnetism, and atomic physics.
Speaker 1: Rick Rodrigues de Mercado, Schmidt Lab
Title: Single-cell stress analysis in spheroids using deformablehydrospheres and cell segmentation
Speaker 2: Jacqueline Labra Muñoz, Huber Lab
Title: A new perspective into the magnetism of ferritin
Room: EM109 (New Gorlaeus building)
Title: Defect-mediated force generation in cellular nematics
Abstract: Tissue reshaping during embryogenesis, cell extrusion events in the gut or tumour growth are crucial biological processes that rely on large-scale mechanical patterns powered by forces from hundreds of cells. To organize these forces, nature has refined a wide palette of biochemical and mechanical cues able to organize single cells into collectively behaving groups. In tissues composed of elongated cells,the organization of these forces strongly depends on the orientational (nematic) order of cells and the presence of topological defects, which are discontinuities in the orientation field. On the one hand, nematic order directs migration of single cells throughout these tissues. On the other hand, robust arrangements of orientation around topological defect cores lead to reproducible force patterns at large scales. Here I will show how cellular topological defects are able to organize unique patterns of force, providing cellular nematics with fine mechanical tools for controlling tissue remodelling.
Duane and Barbara LaViolette Professor of Chemistry
University of Washington, Seattle
(currently on sabbatical with Marileen Dogterom’s lab at TU Delft)
Two mysteries in 2D phase separation: What drives large-scale phase separation in yeast
membranes, and what controls the length scale of small domains in model membranes?
At a particular stage in the growth cycle of yeast, membranes of the vacuole (an organelle) phase
separate. Here, we show that yeast actively tune the transition temperature of their vacuole
membranes to be close to the yeast's growth temperature, which implies that the membrane's
proximity to the miscibility transition is important for the cell's function. Indeed, in yeast,
demixing of vacuole membranes into large, micron-scale domains is correlated with cell survival
through extended periods of low nutrients. In living cells and artificial systems alike, phase-
separated membranes frequently have excess area (more membrane than is needed to enclose the
volume), which leads to patterns of dots or stripes. A persistent open question in the field is
what physical mechanisms give rise to these patterns. Here we show which aspects of current
theories of pattern formation are supported by our data, and where opportunities lie for
developing new models.
Sarah L. Keller, the Duane and Barbara LaViolette Professor of Chemistry, is a biophysicist in
the U.S. at the University of Washington in Seattle. She investigates self-assembly, complex
fluids, and soft matter systems. Her research group’s primary focus concerns how lipid mixtures
within bilayer membranes give rise to complex phase behaviour. She is a Fellow of the American
Physical Society and a Fellow of the Biophysical Society.
Speaker 1: Jacco Ton, Orrit Lab
Title: Progress towards label-free detection of single nano-particles in a dielectrophoretic trap
Speaker 2: Jeremy Ernst, Van Noort Lab
Title: Single-pair FRET reveals nucleosome dynamics in folded chromatin fibers
Muhittin Mungan: Institute of Biological Physics, U. of Cologne
Title: Memory Formation in Driven Disordered Systems
Abstract: Memory formation and ageing are abundant in many soft matter systems. The disorder underlying these
systems gives rise to a rich energy landscape, consisting of a large number of metastable states.
These landscapes are accompanied by a plethora of pathways, along which such systems can evolve when exposed to a
varying temperature or mechanical load. The resulting dynamics can be rather complex. For example,
a crumpled sheet of paper, can evolve under periodic compression into a cyclic response
that is characterized by a hierarchy of nested response-cycles. Often such a response is
realized through the emergence of a system of spatially localized bi-stable mechanical elements, which in turn
can be regarded as constituting a memory of the loading. In this talk I will present a general framework to analyze
the dynamics and memory formation of driven disordered systems.
Title: Counting, Memory and Information Processing in a Mechanical Metamaterial
Abstract: Mechanical Metamaterials use their internal structure to realize desired material properties not seen in nature, including anomalous elastic properties and spatially textured shapemorphing. So far, these materials react directly to mechanical input. Here we introduce metamaterials whose configuration is updated sequentially and that store a memory of the number of compressive cycles in the past: materials that count. Combining counters, we realize complex metamaterials that store multiple memories and that filter sequential input: materials that detect sequential passwords. Our platform is scalable and extendable, and opens a new route towards computation in materia.
Title: Self Assembly of Rigid and Flexible Colloidal Molecules.
Abstract: Colloidal molecules are promising building blocks for assembling larger structures, but their preparation in precise forms and sizes is challenging. Here, using experiment and simulation, we show self-assembly of colloidal molecules by exploiting geometric constraints imposed by particle shape and size. Using two different approaches, we create bothflexible and rigid colloidal molecules by assembling finite-sized clusters from spheres (S) and cubes (C). We prepareflexible colloidal molecules by the assembly of spheres and cubes functionalized with complementary DNA linkers that are mobile on the particle surface, andrigid colloidal molecules using oppositely charged spheres and cubes. We obtained high yields of colloidal molecules with valencies (CSn) CS6, CS4, and CS2 depending on the size ratio of the sphere and cube. These colloidal molecules can be used as building blocks for assembling higher-order structures.
Transcriptional control and optimal sensing of regulatory signals
Transcription factor concentrations can be seen as signals that need to be sensed by organisms in order for them to express their genes as precisely as is required during development or during adjustment to different conditions. The low concentration of all the relevant molecules means that these measurements will be noisy. In eukaryotes, a number of proteins and genomic regions contribute to ensuring a precise transcriptional response. Such a response is important especially in embryonic development, where the organism needs to obtain a minimum of information in a limited time in order to generate a complex body plan. I will present our work on how to extract this information for a series of transcription factors in the fly embryo using a “sensing scheme”, called the information bottleneck, which has recently gained popularity in neuroscience and machine learning. Indeed, the sensors we identify with this scheme have important features in common with the fly enhancers. Our method thus provides a complement to mechanistic, bottom-up approaches for understanding why transcriptional elements are structured the way they are. If there is time, I will also discuss issues around optimal sensing given specific mechanistic constraints.
Title: Many fire-ant systems Abstract: Experiments with fire-ant columnsreveal similarities and differences with granular columns. For granularcolumns, we will show that narrowing the column diameter can result in novelbehavior relative to how we think of wider columns, which were studied morethan a century ago by German engineer Janssen; the key is the force-chainstructure. We will then show that fire-ant columns also exhibit force chains;however, as an active granular system, there are apparent fluctuations andactivity within the system. In 2D, these effects become most noticeable andmanifest in the form of activity waves that propagate along the verticaldirection. Ultimately, these waves reflect the existence of activity cycles,whereby the fire-ant system changes “state” from “active”, where all the antsmove, to “inactive”, where a large fraction of the ants cluster and remain stationary.Our findings indicate that while the “active” states correspond to collectivemotion, in the “inactive” states there is clustering reminiscent of amotility-induced attraction resulting from the social interactions between theants.
Title: Many fire-ant systems
Abstract: Experiments with fire-ant columnsreveal similarities and differences with granular columns. For granularcolumns, we will show that narrowing the column diameter can result in novelbehavior relative to how we think of wider columns, which were studied morethan a century ago by German engineer Janssen; the key is the force-chainstructure. We will then show that fire-ant columns also exhibit force chains;however, as an active granular system, there are apparent fluctuations andactivity within the system. In 2D, these effects become most noticeable andmanifest in the form of activity waves that propagate along the verticaldirection. Ultimately, these waves reflect the existence of activity cycles,whereby the fire-ant system changes “state” from “active”, where all the antsmove, to “inactive”, where a large fraction of the ants cluster and remain stationary.Our findings indicate that while the “active” states correspond to collectivemotion, in the “inactive” states there is clustering reminiscent of amotility-induced attraction resulting from the social interactions between theants.
Abstract: Buckling in thin structures is generally considered as a first step towards failure. Instead, we view mechanical and interfacial instabilities in structures as opportunities for scalable, reversible, and robust mechanisms that must first be understood predictively, and then harvested for their function. This new design paradigm – building with instabilities – calls for an improved understanding of instabilities and pattern formation in complex media. Three examples will be presented: (1) fluid-instability based approaches for digitally fabricating geometrically complex uniformly sized structures, (2) flexible fabric-based gripper that contracts radially upon inflation (3) deployable structures inspired by insect wing expansion. The main feature common to these different problems is the prominence of geometry, and its interplay with mechanics, in dictating complex mechanical behavior that is relevant and applicable over a wide range of length scales.