The transit of food through the gastrointestinal tract is critical for nutrient absorption and survival, and the gastrointestinal tract has the ability to initiate motility reflexes triggered by luminal distention. This complex function depends on the crosstalk between extrinsic and intrinsic neuronal innervation within the intestine, as well as local specialized enteroendocrine cells. However, the molecular mechanisms and the subset of sensory neurons underlying the initiation and regulation of intestinal motility remain largely unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in the stomach, small intestine, and colon. Indeed, Piezo2 is directly required to detect colon distension in vivo. Our study unveils the mechanosensory mechanisms that regulate the transit of luminal contents throughout the gut, which is a critical process to ensure proper digestion, nutrient absorption, and waste removal. These findings set the foundation of future work to identify the highly regulated interactions between sensory neurons, enteric neurons and non- neuronal cells that control gastrointestinal motility.

Sensory neurons of the vagus nerve monitor distention and stretch in the gastrointestinal tract. We used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize two vagal sensory neuronal subtypes expressing Prox2 and Runx3. We show that these neuronal subtypes innervate the esophagus where they display regionalized innervation patterns. Electrophysiological analyses showed that they are both low threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis and swallowing in freely behaving animals. Our work reveals the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

The cytoskeleton has the remarkable ability to self-organize into active materials which underlie diverse cellular processes ranging from motility to cell division. Actomyosin is a canonical example of an active material, which generates cellularscale contractility in part through the forces exerted by myosin motors on actin filaments. While the molecular players underlying actomyosin contractility have been well characterized, how cellular-scale deformation in disordered actomyosin networks emerges from filament-scale interactions is not well understood. In this talk, I’ll present work done in collaboration with Sebastian Fürthauer and Nikta Fakhri addressing this question in vivo using the meiotic surface contraction wave seen in oocytes of the bat star Patiria miniata as a model system. By perturbing actin polymerization, we find that the cellular deformation rate is a nonmonotonic function of cortical actin density peaked near the wild type density. To understand this, we develop an active fluid model coarse-grained from filament-scale interactions and find quantitative agreement with the measured data. The model makes further predictions, including the surprising prediction that deformation rate decreases with increasing motor concentration. We test these predictions through protein overexpression and find quantitative agreement. Taken together, this work is an important step for bridging the molecular and cellular length scales for cytoskeletal networks in vivo.

Macromolecular protein complexes perform essential biological functions across life forms. A fundamental, though yet unsolved question in biology is how the function of such complexes is regulated by intracellular or extracellular signals. For instance, we have little understanding of how forces affect multi-protein machines whose function is often mechanical in nature. We address this question by studying the bacterial flagellar motor, a large complex that powers swimming motility in many bacteria. This rotary motor autonomously adapts to changes in mechanical load by adding or removing force-generating ‘stator’ units that power rotation. In the bacterium Escherichia coli, up to 11 units drive the motor at high load while all the units are released at low load. We manipulate motor load using electrorotation, a technique in which a rapidly rotating electric field applies an external torque on the motor. This allows us to change motor load at will and measure the resulting stator dynamics at single-unit resolution. We found that the force generated by the stator units controls their unbinding, forming a feedback loop that leads to autoregulation of the assembly. We complemented our experiments with theoretical models that provide insight into the underlying molecular interactions. Torque-dependent remodeling takes place within seconds, making it a highly responsive control mechanism, one that is mediated by the mechano-chemical tuning of protein interactions.

We have characterised the motility of the swimming microalga Chlamydomonas reinhardtii as a function of day/night cycles, to which the microalgal growth is entrained. Intriguingly, we find that the microalgae swim almost twice as fast during the night than during the day. I will connect this result with the bioenergetics of flagellar propulsion, discussing consequences for the distributions of cells in lab-based and environmental water columns.

While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Direct visualization enables us to reveal a new mode of motility exhibited by individual cells, in stark contrast to the paradigm of run-and-tumble motility, in which cells are intermittently and transiently trapped as they navigate the pore space; further, analysis of these dynamics enables prediction of single-cell transport over large length and time scales. Moreover, we show that concentrated populations of E. coli can collectively migrate through a porous medium—despite being strongly confined—by chemotactically “surfing” a self-generated nutrient gradient. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter.

Euglena gracilis is an interesting unicellular protist, also because it can adopt different motility strategies: swimming by flagellar propulsion, or crawling thanks to large amplitude shape changes of the whole body (a behavior known as “metaboly”, or “amoeboid motion”). Swimming trajectories are helical. The are powered by the beating of a single emerging flagellum, which spans non-planar waveforms in the shape of a twisted lasso. Finally the harmoniously coordinated shape changes that make metaboly possible, reminiscent of peristaltic waves, arise form the relative sliding of its pellicle strips, resulting in twisted helical bundles. We will report on the most recent findings on these interconnected topics, for which helical shapes provide a striking fil rouge.

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

Bacteria exhibit a bewildering diversity of morphologies, but despite their impact on nearly all aspects of life, they are frequently classified into a few general categories, usually just “spheres” and “rods.” Curved-rod bacteria are one simple variation observed in many environments, particularly the ocean. However, why so many species have evolved this shape is unknown. We used a regularized Stokeslet Boundary Element Method to model the motility of flagellated, curved bacteria. We show that curvature can increase swimming efficiency, revealing a widely applicable selective advantage. Furthermore, we show that the distribution of cell lengths and curvatures observed across bacteria in nature is predicted by evolutionary trade-offs between three tasks influenced by shape: efficient swimming, the ability to detect chemical gradients, and reduced cost of cell construction. We therefore reveal shape as an important component of microbial fitness.

A key challenge in modern soft matter is to identify the principles that govern the organisation and functionality in non-equilibrium systems. Current research efforts largely focus on non-equilibrium processes that occur either at the single-molecule scale (e.g. protein and DNA conformations under driving forces), or at the scale of whole tissues, organisms, and active colloidal and microscopic objects. However, the range of the scales in-between — from molecules to large-scaled molecular assemblies that consume energy and perform work — remains under-explored. This is, nevertheless, the scale that is crucial for the function of a living cell, where molecular self-assembly driven far from equilibrium produces mechanical work needed for cell reshaping, transport, motility, division, and healing. Today I will discuss physical modelling of active elastic filaments, called ESCRT-III filaments, that dynamically assemble and disassemble on cell membranes. This dynamic assembly changes the filaments’ shape and mechanical properties and leads to the remodelling and cutting of cells. I will present a range of experimental comparisons of our simulation results: from ESCRT-III-driven trafficking in eukaryotes to division of evolutionary simple archaeal cells.

Bacterial motility is central to processes in agriculture, the environment, and medicine. While motility is typically studied in homogeneous environments, many bacterial habitats—e.g., soils, sediments, and biological gels/tissues—are heterogeneous porous media. Here, through studies of E. coli in transparent 3D porous media, we demonstrate that confinement in a heterogeneous medium fundamentally alters motility. In particular, we show how the paradigm of run-and-tumble motility is dramatically altered by pore-scale confinement, both for cells performing undirected motion and those performing chemotaxis, directed motion in response to a chemical stimulus. Our porous media also enable precisely structured multi-cellular communities to be 3D printed. Using this capability, we show how confinement-dependent chemotaxis enables populations to stabilize large-scale perturbations in their overall morphology. Together, our work thus reveals new principles to predict and control the behavior of bacteria, and active matter in general, in heterogeneous environments.

The coordinated migration of groups of cells underlies many biological processes, including embryo development, wound healing and cancer metastasis. In many of these situations, tissues are able to tune themselves between liquid-like states, where cells flow collectively as in a liquid, and solid-like states that can support shear stresses. In this talk I will describe mesoscopic models of cell assemblies inspired by active matter physics to examine the roles of cell motility, cell crowding and the interplay of contractility and adhesion in controlling the rheological state of biological tissue.

Motility is a crucial virulence factor for many species of bacteria, but it is not fully understood how bacterial motility is practically involved in pathogenicity. This time I will give a talk on the association of motility with pathogenicity in the zoonotic spirochete bacterium Leptospira. Recently, we measured swimming force of individual leptospires using optical tweezers and found that they can generate ~30 times of the swimming force of E. coli. We also observed that leptospires increase the reversal frequency of swimming at the gel-liquid interface, resembling host dermis exposed to contaminated water (Abe et al., 2020, Sci Rep). These could be involved in percutaneous infection of the spirochete. We have shown that Leptospira not only swims in liquid but also moves over solid surfaces (Tahara et al., 2018, Sci Adv). We quantified the surface motility called “crawling” on cultured kidney tissues from various mammals, showing that pathogenic leptospires crawl over the tissue surfaces more persistently that non-pathogenic ones (Xu et al., 2020, Front Microbiol). I will discuss the spirochete motility related to pathogenicity from the biophysical viewpoint.

It is often assumed that biological swimmers conform faithfully to certain stereotypes assigned to them by physicists and mathematicians, when the reality is in fact much more complicated. In this talk we will use a combination of theory, experiments, and robotics, to understand the physical and evolutionary basis of motility control in a number of distinguished organisms. These organisms differ markedly in terms of their size, shape, and arrangement of locomotor appendages, but are united in their use of cilia - the ultimate shape-shifting organelle - to achieve self-propulsion and navigation.

Understanding individual and macroscopic transport properties of motile micro-organisms in complex environments is a timely question, relevant to many ecological, medical and technological situations. At the fundamental level, this question is also receiving a lot of attention as fluids loaded with swimming micro-organisms has become a rich domain of applications and a conceptual playground for the statistical physics of “active matter”. The existence of microscopic sources of energy borne by the motile character of these micro-swimmers is driving self-organization processes at the origin of original emergent phases and unconventional macroscopic properties leading to revisit many standard concepts in the physics of suspensions. In this presentation, I will report on a recent exploration on the question of spontaneous formation of large scale collective motion in relation with the rheological response of active suspensions. I will also present new experiments showing how the motility of bacteria can be controlled such as to extract work macroscopically.

Archaea have evolved to survive in some of the most extreme environments on earth. Life in extreme, nutrient-poor conditions gives the opportunity to probe fundamental energy limitations on movement and response to stimuli, two essential markers of living systems. Here we use three-dimensional holographic microscopy and computer simulations to show that halophilic archaea achieve chemotaxis with power requirements one hundred-fold lower than common eubacterial model systems. Their swimming direction is stabilised by their flagella (archaella), enhancing directional persistence in a manner similar to that displayed by eubacteria, albeit with a different motility apparatus. Our experiments and simulations reveal that the cells are capable of slow but deterministic chemotaxis up a chemical gradient, in a biased random walk at the thermodynamic limit.