Physics of Life seminars

Cells and microorganisms are motile, yet the stationary nature of conventional microscopes impedes comprehensive, long-term behavioral and biomechanical analysis. The limitations are twofold: a narrow focus permits high-resolution imaging but sacrifices the broader context of organism behavior, while a wider focus compromises microscopic detail. This trade-off is especially problematic when investigating rapidly motile ciliates, which often have to be confined to small volumes between coverslips affecting their natural behavior. To address this challenge, we introduce Trackoscope, an 2-axis autonomous tracking microscope designed to follow swimming organisms ranging from 10μm to 2mm across a 325 square centimeter area for extended durations—ranging from hours to days—at high resolution. Utilizing Trackoscope, we captured a diverse array of behaviors, from the air-water swimming locomotion of Amoeba to bacterial hunting dynamics in Actinosphaerium, walking gait in Tardigrada, and binary fission in motile Blepharisma. Trackoscope is a cost-effective solution well-suited for diverse settings, from high school labs to resource-constrained research environments. Its capability to capture diverse behaviors in larger, more realistic ecosystems extends our understanding of the physics of living systems. The low-cost, open architecture democratizes scientific discovery, offering a dynamic window into the lives of previously inaccessible small aquatic organisms.

Sijbren Otto explores how features associated with life can arise from initially lifeless chemical components. The systems couple reversible oligomerization of comparatively simple molecular building blocks with self-assembly. Their behavior includes the spontaneous appearance of self-replicating molecules, catalytic activity extending beyond autocatalysis, and the breaking of chiral symmetry. These observations connect the emergence of molecular replication and catalysis with the origins of biological handedness.

Living systems select one molecular handedness, making the origin of homochirality a central problem in understanding how life began. David Lacoste examines how this asymmetry can emerge in autocatalytic chemical networks when they contain sufficiently many chiral species and operate far from equilibrium. Polymerization greatly expands molecular diversity, raising the question of whether it can also generate and preserve a preference for one handedness. The talk develops this connection through an RNA reactor model, studying the conditions under which template-directed ligation and polymerization produce and maintain homochirality.

The emergent dynamics exhibited by collections of living organisms often shows signatures of symmetries that are broken at the single-organism level. At the same time, organism development itself encompasses a well-coordinated sequence of symmetry breaking events that successively transform a single, nearly isotropic cell into an animal with well-defined body axis and various anatomical asymmetries. Combining these key aspects of collective phenomena and embryonic development, we describe here the spontaneous formation of hydrodynamically stabilized active crystals made of hundreds of starfish embryos that gather during early development near fluid surfaces. We describe a minimal hydrodynamic theory that is fully parameterized by experimental measurements of microscopic interactions among embryos. Using this theory, we can quantitatively describe the stability, formation and rotation of crystals and rationalize the emergence of mechanical properties that carry signatures of an odd elastic material. Our work thereby quantitatively connects developmental symmetry breaking events on the single-embryo level with remarkable macroscopic material properties of a novel living chiral crystal system.

Biological materials gain complexity from the programmable nature of their components. To manufacture materials with comparable complexity synthetically, we need to create building blocks with low crosstalk so that they only bind to their desired partners. Canonically, these building blocks are made using DNA strands or proteins to achieve specificity. Here we propose a new materials platform, termed Magnetic Handshake Materials, in which we program interactions through designing magnetic dipole patterns. This is a completely synthetic platform, enabled by magnetic printing technology, which is easier to both model theoretically and control experimentally. In this seminar, I will give an overview of the development of the Magnetic Handshake Materials platform, ranging from interaction, assembly to function design.

An equation of state is something you hear about in introductory thermodynamics, for example, the Ideal gas equation. The ideal gas equation relates the pressure, volume, and the number of particles of the gas, to its temperature, uniquely defining its state. This description is possible in physics when the system under investigation is in equilibrium or near equilibrium. In biology, a tissue is modeled as a fluid composed of cells. These cells are constantly interacting with each other through mechanical and chemical signaling, driving them far from equilibrium. Can an equation of state exist for such a messy interacting system? In this talk, I show that the presence of strong cell-cell interaction in tissues gives rise to a novel non-equilibrium, size-dependent surface tension, something unheard of for classical fluids. This surface tension, in turn, modifies the packing of cells inside the tissue generating a size-dependent density and pressure. Finally, we show that a combination of these non-equilibrium pressure and densities can yield an equation of state for biological tissues arbitrarily far from equilibrium. In the end, I discuss how this new paradigm of size-dependent biological properties gives rise to novel modes of cellular motion in tissues

The fusion of cell aggregates widely exists during biological processes such as development, tissue regeneration, and tumor invasion. Cellular spheroids (spherical cell aggregates) are commonly used to study this phenomenon. In previous studies, with approximated assumptions and measurements, researchers found that the fusion of two spheroids with some cell type is similar to the coalescence of two liquid droplets. However, with more accurate measurements focusing on the overall shape evolution in this process, we find that even in the previously-regarded liquid-like regime, the fusion process of spheroids can be very different from regular liquid coalescence. We conduct numerical simulations using both standard particulate models and vertex models with both Molecular Dynamics and Brownian Dynamics. The simulation results show that the difference between spheroids and regular liquid droplets is caused by the microscopic overdamped dynamics of each cell rather than the topological cell-cell interactions in the vertex model. Our research reveals the necessity of a new continuum theory for “liquid” with microscopically overdamped components, such as cellular and colloidal systems. Detailed analysis of our simulation results of different system sizes provides the basis for developing the new theory.

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.

Active matter describes a class of systems that are maintained far from equilibrium by driving forces acting on the constituent particles. Here I will focus on confined active nematics, which exhibit especially rich flow behavior, ranging from structured patterns in space and time to disordered turbulent flows. To understand this behavior, I will take a deterministic dynamical systems approach, beginning with the hydrodynamic equations for the active nematic. This approach reveals that the infinite-dimensional phase space of all possible flow configurations is populated by Exact Coherent Structures (ECS), which are exact solutions of the hydrodynamic equations with distinct and regular spatiotemporal structure; examples include unstable equilibria, periodic orbits, and traveling waves. The ECS are connected by dynamical pathways called invariant manifolds. The main hypothesis in this approach is that turbulence corresponds to a trajectory meandering in the phase space, transitioning between ECS by traveling on the invariant manifolds. Similar approaches have been successful in characterizing high Reynolds number turbulence of passive fluids. Here, I will present the first systematic study of active nematic ECS and their invariant manifolds and discuss their role in characterizing the phenomenon of active turbulence.

Our world is full of living creatures that must share information to survive and reproduce. As humans, we easily forget how hard it is to communicate within natural environments. So how do organisms solve this challenge, using only natural resources? Ideas from computer science, physics and mathematics, such as energetic cost, compression, and detectability, define universal criteria that almost all communication systems must meet. We use insect swarms as a model system for identifying how organisms harness the dynamics of communication signals, perform spatiotemporal integration of these signals, and propagate those signals to neighboring organisms. In this talk I will focus on two types of communication in insect swarms: visual communication, in which fireflies communicate over long distances using light signals, and chemical communication, in which bees serve as signal amplifiers to propagate pheromone-based information about the queen’s location.

Diverse physical processes played important roles in the origin of life. I will review the origin of molecular homochirality, the growth of protocell membranes, and potential roles for liquid-liquid phase separation. I will then discuss the concept of functional information and its quantitative relationship with molecular function.

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.

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.

Interfaces and membranes are ubiquitous in cellular systems across various scales. From lipid membranes to the interfaces of biomolecular condensates inside the cell, these borders not only protect and segregate the inner components from the outside world, but also are actively participating in mechanical regulation and biochemical reaction of the cell. Being part of a living system, these interfaces (membranes) are usually active and away from equilibrium. Yet, it's still not clear how activity can tweak their equilibrium dynamics. Here, I will introduce a model system to tackle this problem. We put together a passive fluid and an active nematics, and study the behavior of this liquid-liquid interface. Whereas thermal fluctuation of such an interface is too weak to be observed, active stress can easily force the interface to fluctuate, overhang, and even break up. In the presence of a wall, the active phase exhibits superfluid-like behavior: it can climb up walls -- a phenomenon we call activity-induced wetting. I will show how to formulate theories to capture these phenomena, highlighting the nontrivial effects of active stress. Our work not only demonstrates that activity can introduce interesting features to an interface, but also sheds light on controlling interfacial properties using activity.

The spontaneous collective motion of self-propelled agents is ubiquitous in the natural world, and it often occurs in complex environments, be it bacteria and cells migrating through polymeric extracellular matrix or animal herds and human crowds navigating structured terrains. Much is known about flocking dynamics in pristine backgrounds, but how do spatio-temporal heterogeneities in the environment impact such collective self-organization? I will present two model systems, a colloidal active fluid negotiating disordered obstacles and a confined dense bacterial suspension in a viscoelastic medium, as controllable platforms to explore this question and highlight general mechanisms for active self-organization in complex environments. By combining theory and experiment, I will show how flocks on disordered substrates organize into a novel dynamic vortex glass phase, akin to vortex glasses in dirty superconductors, while the presence of viscoelasticity can calm the otherwise turbulent swarming of bacteria, allowing the emergence of a large scale coherent and even oscillatory vortex when confined on the millimetre scale.

Living cells contain millions of enzymes and proteins, which carry out multiple reactions simultaneously. To optimize these processes, cells compartmentalize reactions in membraneless liquid condensates. Certain features of cellular condensates can be explained by principles of liquid-liquid phase separation studied in material science. However, biological condensates exist in the inherently out of equilibrium environment of a living cell, being driven by force-generating microscopic processes. These cellular conditions are fundamentally different than the equilibrium conditions of liquid-liquid phase separation studied in materials science and physics. How condensates function in the active riotous environment of a cell is essential for understanding of cellular functions, as well as to the onset of neurodegenerative diseases. Currently, we lack model systems that enable rigorous studies of these processes. Living cells are too complex for quantitative analysis, while reconstituted equilibrium condensates fail to capture the non-equilibrium environment of biological cells. To bridge this gap, we reconstituted a DNA based membraneless condensates in an active environment that mimics the conditions of a living cell. We combine condensates with a reconstituted network of cytoskeletal filaments and molecular motors, and study how the mechanical interactions change the phase behavior and dynamics of membraneless structures. Studying these composite materials elucidates the fundamental physics rules that govern the behavior of liquid-liquid phase separation away from equilibrium while providing insight into the mechanism of condensate phase separation in cellular environments.

Cells and microorganisms produce and consume all sorts of chemicals, from nutrients to signalling molecules. The same happens at the nanoscale inside cells themselves, where enzymes catalyse the production and consumption of the chemicals needed for life. In this work, we have found a generic mechanism by which such chemically-active particles, be it cells or enzymes or engineered synthetic colloids, can "sense" each other and ultimately self- organize in a multitude of ways. A peculiarity of these chemical-mediated interactions is that they break action-reaction symmetry : for example, one particle may be repelled from a second particle, which is in turn attracted to the first one, so that it ends up "chasing" it. Such chasing interactions allow for the formation of large clusters of particles that "swim" autonomously. Regarding enzymes, we find that they can spontaneously aggregate into clusters with precisely the right composition, so that the product of one enzyme is passed on, without lack or excess, to the next enzyme in the metabolic cascade.

A key question for basic biology and regenerative medicine concerns the way in which evolution exploits physics toward adaptive form and function. While genomes specify the molecular hardware of cells, what algorithms enable cellular collectives to reliably build specific, complex, target morphologies? Our lab studies the way in which all cells, not just neurons, communicate as electrical networks that enable scaling of single-cell properties into collective intelligences that solve problems in anatomical feature space. By learning to read, interpret, and write bioelectrical information in vivo, we have identified some novel controls of growth and form that enable incredible plasticity and robustness in anatomical homeostasis. In this talk, I will describe the fundamental knowledge gaps with respect to anatomical plasticity and pattern control beyond emergence, and discuss our efforts to understand large-scale morphological control circuits. I will show examples in embryogenesis, regeneration, cancer, and synthetic living machines. I will also discuss the implications of this work for not only regenerative medicine, but also for fundamental understanding of the origin of bodyplans and the relationship between genomes and functional anatomy.

Active particles which are self-propelled by converting energy into mechanical motion represent an expanding research realm in physics and chemistry. For micron-sized particles moving in a liquid (``microswimmers''), most of the basic features have been described by using the model of overdamped active Brownian motion [1]. However, for macroscopic particles or microparticles moving in a gas, inertial effects become relevant such that the dynamics is underdamped. Therefore, recently, active particles with inertia have been described by extending the active Brownian motion model to active Langevin dynamics which include inertia [2]. In this talk, recent developments of active particles with inertia (``microflyers'', ``hoppers'' or ``runners'') are summarized including: inertial delay effects between particle velocity and self-propulsion direction [3], tuning of the long-time self-diffusion by the moment of inertia [3], the influence of inertia on motility-induced phase separation and the cluster growth exponent [4], and the formation of active micelles (“rotelles”) by using inertial active surfactants. References [1] C. Bechinger, R. di Leonardo, H. Löwen, C. Reichhardt, G. Volpe, G. Volpe, Reviews of Modern Physics 88, 045006 (2016). [2] H. Löwen, Journal of Chemical Physics 152, 040901 (2020). [3] C. Scholz, S. Jahanshahi, A. Ldov, H. Löwen, Nature Communications 9, 5156 (2018). [4] S. Mandal, B. Liebchen, H. Löwen, Physical Review Letters 123, 228001 (2019). [5] C. Scholz, A. Ldov, T. Pöschel, M. Engel, H. Löwen, Surfactants and rotelles in active chiral fluids, will be published

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.