Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session S11: Collective Behaviors in Biology IFocus
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Sponsoring Units: DBIO Chair: Andrew Mugler, University of Pittsburgh Room: Room 203 |
Thursday, March 9, 2023 8:00AM - 8:36AM |
S11.00001: Bacterial biofilms as model tissues Invited Speaker: Vasily Zaburdaev Ability of bacteria to generate and utilise mechanical forces is pronounced through their whole life cycle. Individual cells deploy forces to attach and move on surfaces. Moving and interacting, bacteria find each other and form microcolonies that consist of several thousands of cells and are held together by a network of active, retractile cell appendages. Such microcolonies are often the functional units of the bacterial existence in natural settings and in the context of disease. We introduce theoretical framework describing the bacterial microcolonies as active viscoelastic materials. We can show that the forces experienced by the cells during colony formation may determine their differentiation and the resistance of the microcolony to the effect of antibiotics. We will discuss how this theory might be also useful in eukaryotic systems such as organoids, tumour spheroids or clustering immune cells. Microcolonies may further develop into even more complex differentiated bacterial communities known as biofilms. There, bacteria embed themselves in the self-secreted extracellular matrix creating an analogue of multicellular tissues. We will outline some future research avenues deepening this analogy and illustrate it with an intriguing example of wound healing in bacterial biofilms. |
Thursday, March 9, 2023 8:36AM - 8:48AM |
S11.00002: Collective effects in flow-driven cancer cell migration Louis Gonzalez, Andrew Mugler Various cancer cell types have been shown to migrate in the direction of fluid flow via a process called autologous chemotaxis, in which cells secrete and detect molecules that are biased by the flow. This process is thwarted at high cell density because molecules from other cells interfere with a given cell's signal. Using a minimal model of autologous chemotaxis, we determine the cell density at which sensing fails, and we find that it agrees with published experimental measurements. We derive a physical limit to autologous chemotaxis in terms of the cell density, the Péclet number, and the length scales of the cell and its environment. Motivated by the ability of cancer cells to migrate in clusters, we explore the possibility that cells can overcome this physical limit by detecting the flow direction collectively. We demonstrate using theory and simulations that collective autologous chemotaxis is optimal at high cell densities and is realizable using concentration sensing, gradient sensing, and cell-cell repulsion, all ubiquitous cell capabilities. Our results shed light on an important sensory strategy employed by cancer cells in dense tumor environments. |
Thursday, March 9, 2023 8:48AM - 9:00AM |
S11.00003: Motility Induced Phase Separation of deformable cells Austin Hopkins, Benjamin Loewe, M Cristina Marchetti Unlike passive systems, which require attractive interactions to phase separate, active systems with purely repulsive interactions can phase separate via a process called motility-induced phase separation (MIPS). There has been much interest in how particle properties like shape and interaction softness, as well as system properties like polydispersity and cell-division affect MIPS. Much previous work, however, has focused on rigid particles, even though the cells that make up biological systems can significantly deform when closely packed. Using a multi-phase field model, we examine how particle deformability, which is a proxy for cell stiffness, affects MIPS. We find that the effect of deformability on phase separation can be understood as a modification to the effective density, with higher deformability corresponding to a lower effective density. In addition, the dense regions become increasingly disordered as deformability increases. Our results contextualize the applicability of MIPS to biological systems and have implications for how cells in biological systems may self-organize. |
Thursday, March 9, 2023 9:00AM - 9:12AM |
S11.00004: Geometric programming of collective sensing of neural cells Guanyu Li, Bo Sun, Andrew Mugler, Patrick Chappell, Ryan W LeFebre, Alia Starman To maintain the normal functionality of multicellular organisms, cells will integrate the chemical or physical information sensed by receptors and respond collectively through information networks constructed by intercellular communication methods, for example, gap junctions, secreted factors, etc. This process, even though it is vital for maintaining normal biological processes, is still far from fully understood. In our research, we used cell micropatterning techniques to pattern cell colonies on a grid-shaped maze and we control the connection between each grid by narrow bridges occupied by a small number of cells. The design of experiments enabled us to manipulate the information pathway that cells use to communicate. We will investigate the cellular response under external chemical stimulation. |
Thursday, March 9, 2023 9:12AM - 9:24AM |
S11.00005: Sensitivity in the cochlea through local tuning rules Asheesh S Momi, Isabella R Graf, Julian A Rubinfien, Benjamin B Machta The auditory range of the human ear spans over a trillion-fold range in sound intensity and ten octaves of frequency. Sound is converted into a surface wave along the basilar membrane whose mechanical properties lead to a frequency-dependent resonant position. Along this basilar membrane, embedded hair cells sense small displacements and transduce them into electrical signals. It is commonly believed that these hair cells operate near a so-called Hopf bifurcation crucial to their enormous dynamic range. However, hair cells are only a small perturbation to the mechanical properties of the basilar membrane. While the state of an individual hair cell influences the mechanics of every frequency mode, they can only sense local displacements of the basilar membrane dominated by a narrow frequency band. How these hair cells, acting individually, can tune the entire cochlea to be sensitive to all frequencies remains an open question. Here we present a model where hair cells use only local information, their mean squared displacement in response to thermal noise, to tune the entire cochlea to an array of critical modes. This feedback scheme, agnostic to precise molecular details, can robustly tune the cochlea’s modes to criticality even in the presence of perturbations. This work illuminates how individual hair cells can collectively create a critical cochlea rather than being independently tuned. |
Thursday, March 9, 2023 9:24AM - 9:36AM |
S11.00006: Nuclei size-regulated packing and phase transition on multicellular spheres Wenhui Tang, Jessie Huang, Darrell N Kotton, Dapeng Bi, Ming Guo Within curved epithelia of multicellular systems, cells arrange differently to form various structures and perform functions. These diversities can be due to topology, cell layer thickness, and various mechanical perturbations. However, the fundamental mechanisms of how cells regulate local packing within these curved multicellular epithelia which gives rise to global architecture is not clear. Furthermore, how their packing evolve during growth and development remains unknown. Here by performing experiments using human iPSC-derived lung alveolospheres and numerical simulation, we show that nuclei-to-cell size ratio regulate both epithelial local neighbor orders and phases. As alveolospheres grow bigger, the nuclei-to-cell ratio increases, resulting in more ordered cellular packing and a topological gas-to-liquid transition. This is because cell nuclei set the lower limit of cell-cell distance and thus prevent the cell collision. In simulation by setting smallest cell-cell distance ratio as cell nuclei ratios, we are able to reproduce the alveolospheres packing evolution during entire growth stages. By further artificially applying osmotic shock to increase the nuclei-to-cell size ratio in alveolospheres, we indeed observe that the cell packing become more ordered. Together, our finding highlights the importance of cell nuclei in regulating both nearest neighbor order and epithelia phases during the growth of alveolospheres. This finding also has the potential to identify the stages and physical phases of other developmental and structure formation processes, such as morphogenesis. |
Thursday, March 9, 2023 9:36AM - 9:48AM |
S11.00007: Long-range cellular wound response manifests as ebb and flow Sun-Min Yu, Myeonggon Park, Yitan Li, Steve Granick We inquire into communication at longer range than can be explained by current understanding of cell extrusion as the joint contribution of pulse-string and lamellipodium at the interface between an extruding cell and its neighbors. Our live-cell optical imaging reveals collective tissue-scale movement provided that damage (from micro-patterned strong laser irradiation) is at multiple spots. With time, bulk elastic behavior causes these multiple spots to merge into a single spot: with inward flow towards the damage at early times, followed by later outward flow, mediated by actomyosin contractility. Using a knock-down expression model, we confirm that this in turn is modulated by mechanosensitive channels, Piezo1 and TRPC1, and also by calcium propagation kinetics. |
Thursday, March 9, 2023 9:48AM - 10:00AM |
S11.00008: Local vs Central Nervous System control of Hindgut Motility Spandan Pathak, Norma Peña-Flores, Phillip Alvarez, Jenna Feeley, Jens Herberholz, Wolfgang Losert Motility is a critical function of the gastrointestinal (GI) system governed by multiple neurogenic and myogenic processes. Several overlapping mechanisms have evolved for its regular operation including modulation by the Central Nervous System (CNS), Enteric Nervous System (ENS), and intrinsic pacemaker cells. These processes remain poorly understood since mammalian species offer limited accessibility. Crayfish provides an accessible ex vivo model to study the interplay between CNS regulation and neurochemical control of GI motor patterns. In this talk, we will discuss the effects of CNS denervation and exogenously applied serotonin (5-HT) on hindgut motility. Multiscale measurements showed motility parameters mostly comprised seconds-scale waves, that remained stable throughout 90 minutes of control conditions. Eliminating CNS innervation reduced wave power and movement coordination, but did not affect frequency or wave direction. Subsequent application of 5-HT increased wave power and directional switching, but failed to restore synchronized movement, indicating that exogenous serotonin does not fully compensate for the loss of CNS regulation. Our model provides a multiscale analysis framework to connect CNS and interrelated neurochemistry to GI motor dynamics. |
Thursday, March 9, 2023 10:00AM - 10:12AM |
S11.00009: Gut Instincts: A data driven approach to mouse colon modeling Andrea J Welsh, Kristen Smith-Edwards, Brian Davis, Bard Ermentrout Colon motility, the spontaneous self-generated movement and motion of the colon muscle and its cells, is produced by activity in different types of cells such as myenteric neurons of the enteric nervous system (ENS), neurons of the autonomic nervous system (ANS) and interstitial cells of Cajal (ICC). Two colon motor patterns measured experimentally are motor complexes (MC) often associated with the propulsion of fecal contents, and ripple contractions which are involved in mixing and absorption. How ICC and neurons of the ENS and ANS interact to initiate and influence colon motility is still not completely understood. This makes it difficult to develop new therapies to restore function in pathological conditions. This talk will discuss statistical analysis of the optogenetic and calcium measurements of mouse colons and how it is implemented in the data-driven modeling of the ICCs and neurons that also capture the global dynamics that are observed in the colon. |
Thursday, March 9, 2023 10:12AM - 10:24AM |
S11.00010: Emergent bacterial dynamics in self-generated oxygen gradients Babak Vajdi Hokmabad, Sebastian Gonzales La Corte, Sujit S Datta In many biological and environmental settings, e.g. mucus in the lungs and subsurface porous media, bacterial populations are strongly confined in tight spots where oxygen availability is spatially variable. How do such variations in oxygen supply influence the collective behavior of a population of motile bacteria? To address this question, here, we experimentally study how bacterial suspensions react to self-generated oxygen gradients in micro-confinement. We find that the coupling between cellular motility and the local oxygen concentration gives rise to the formation of a dense, immotile phase that coexists with a less dense, highly motile phase in a manner reminiscent of Motility-Induced Phase Separation (MIPS). Furthermore, we show how the active turbulence generated by the motile phase can result in large-scale fluctuations at the interface between both phases, enhancing oxygen influx and thus subsequent propagation of this interface. Finally, we show how these collective dynamics are markedly altered in a complex fluid akin to airway mucus. Altogether, our work reveals the rich collective dynamics that can emerge for bacterial populations in environments with physicochemical complexity. |
Thursday, March 9, 2023 10:24AM - 10:36AM |
S11.00011: Cooperative T4 Phage Resistance in E. coli Robert H Austin, Krisztina Nagy, Trung V Phan, Ryan Morris, Julia Bos, Peter Galajda Studies by Delbruck and Luria of the resistance of the common bacteria E. coli to bacteriophages ushered in the age of quantitive molecular biology. The sophisticated analysis using colony number fluctuation ``jackpots’’ was used to support the assumption of the authors that resistance to phage occurred in previous generations of bacteria by random chance, and not by exposure to the phage. This presumably put a stake in heart of the Lamarckian hypothesis of acquired phenotypes, and so it is taught in countless introductory biology courses. |
Thursday, March 9, 2023 10:36AM - 10:48AM |
S11.00012: The interplay of behavioral variability and response sensitivity generates collective effects in host-pathogen transmission dynamics Sounok Ghosh, J. M Schwarz, Antun Skanata Social interactions have been shown to drive pathogen transmission in a host population even under the most stringent conditions. For example, areas under strict Covid-19 lockdowns showed long-tailed incidence curves. It is now recognized that behavioral stochasticity, manifest at the individual level, can dynamically generate a range of transmission patterns, such as waves and plateaus. Yet, strategies seeking to mitigate the effects of an epidemic require collective behavioral changes. Implementing these in the face of noise, reduced sensitivity and nonlinear feedback is key to a successful public health policy. Here we present a model of pathogen transmission that ties individual behaviors to population-level phenomena. We find that periodic and robust collective changes in behavior drive pathogen prevalence across the population in a wave-like pattern. By incorporating gradual adjustments in behavior through feedback mechanisms we find trade-offs between response sensitivity and behavioral noise, which can be used to mount an efficient strategy at early times in the outbreak. Our models can be applied to a range of human pathogens, and benchmarked against data (wastewater surveillance, hospitalizations, and mobility) to generate predictions for broad policy recommendations. |
Thursday, March 9, 2023 10:48AM - 11:00AM |
S11.00013: Curvature-mediated bridging drives non-adhesive strip wound healing Hongmei Xu Wound healing through re-epithelialization of gaps is of tremendous importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse string constriction. However, the studies to date have not separated the gap curvature effect from the gap size effect. Here, to investigate the strip edge curvature and strip size effects on the re-epithelialization responses of Madin-Darby canine kidney cells independently, we fabricate fibronectin micropatterned hydrogel substrates with straight and wavy non-cell-adhesive long strips of different radii of curvature and gap widths. Our experiments show that the epithelial cell re-epithelization is closely regulated by the gap geometry: actin cable accumulates at the two ends of straight stripes and drives gap closure via purse string contraction; straight strips do not facilitate cell migration perpendicular to wound front but wavy strips do, through the complex cell movement patterns induced by curved boundaries; cell bulging and lamellipodium extension can help establish bridges over gap widths in certain range, but not significantly beyond; for the gap size that can be bridged in the present study, actin cables can readily form to spread the bridges, leading to full gap closure. Our results can help to guide the development of better wound management strategies in the future. |
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