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 D06: Mechanics of Cells and Tissues IIFocus
|
Hide Abstracts |
Sponsoring Units: DBIO Chair: Ming Guo, MIT Room: Room 129 |
Monday, March 6, 2023 3:00PM - 3:36PM |
D06.00001: Mechanobiology of Collective Cell Migration under Physical Confinements Invited Speaker: Chwee Teck T Lim Cells migrating in sheets or large cohorts tend to behave very differently from cells migrating individually, especially under geometrical or physical constraints and topography. Such distinctive behavior of cells migrating in a collective manner underlies several important biological processes such as wound closure, maintenance of intestinal epithelium, developmental processes and even cancer metastasis. As such, they can also provide important insights towards better tissue repair and regenerative medicine. Here, we obtained biological insights into the kinematic behavior of collectively migrating cell cohorts under a series of well-defined geometrical and physical confinements such as on narrow strips and on out-of-plane curved surfaces. |
Monday, March 6, 2023 3:36PM - 3:48PM |
D06.00002: Strain Response of Epithelial Cell Trains Toshi Parmar, Liam P Dow, Beth L Pruitt, M Cristina Marchetti Inspired by recent in vitro studies of epithelial monolayers on 1D micro-patterned substrates, we use continuum and mesoscopic models of a linear array of cells to examine their response to externally applied mechanical perturbations. We specifically explore the tissue behavior in response to step-strain and oscillatory perturbations at the boundary. To quantify the interplay between biochemical and mechanical processes, we compare a number of discrete models of cell trains proposed in the literature that incorporate various feedback mechanisms between strain or stress and myosin recruitment, which in turn controls cell-edge tension and tissue contractility. We identify the dependence of the spatial and temporal propagation of mechanical perturbations on cell contractility and cortical tension and characterise the frequency dependent response of the monolayer to oscillatory strains. |
Monday, March 6, 2023 3:48PM - 4:00PM |
D06.00003: Intercellular adhesion mediates non-monotonic growth of cell collectives due to biomechanical feedback Abdul N Malmi Kakkada The growth of cell collectives is governed by the interplay of many physical and biological factors, ranging from intercellular forces to gene expression in individual cells. Even though biomechanical forces arise due to the growth and division of individual cells, little is known about this fundamental aspect of collective cell growth. By implementing a minimal computational model for three-dimensional multicellular spheroids (MCS), we determine how intercellular adhesive interactions and mechanical pressure on single cells regulate cell division. We discover that emergent spatial variations in the cell division rate, with cells at the periphery of the MCS dividing rapidly while cells at the core undergo little to no division, are regulated by intercellular adhesion strength. Varying cell-cell adhesion strength results in non-monotonic MCS growth. A biomechanical feedback mechanism coupling intercellular adhesion strength and microenvironment-dependent pressure experienced by cells determines the onset of a dormant phase, and explains the non-monotonic proliferation response. Our work, which shows that proliferation is regulated by a pressure-adhesion feedback mechanism, maybe a general feature of multicellular growth. |
Monday, March 6, 2023 4:00PM - 4:12PM |
D06.00004: Strain-Tension Feedback Leads to Sustained Pulsing Activity in Epithelial Tissues Sam Banks, Fernanda L Pérez Verdugo, Shiladitya Banerjee Tissue morphogenesis is the result of coordinated deformations of the underlying cells. In vivo, this occurs through the recruitment of myosin motors along cell junctions, which produce contractile forces. Previous work has found that to undergo the permanent deformations required for structure-altering transitions, repeated pulses of myosin activity are necessary. The mechanistic basis of this tissue-wide pulsing activity remains unknown. To capture this phenomenon, we have developed a vertex model of epithelial tissues with mechanochemical feedback, where junctional active tension is controlled by junction strain. In our model, a junction is activated when it is stretched beyond a threshold strain, and deactivated when it is contracted beyond a minimum strain or an activation lifetime is reached due to actomyosin turnover. These feedback rules reflect mechanosensitive rates of actomyosin assembly and disassembly. This mechanochemical model produces tissues which can remodel through self-sustaining tension pulses that cause junction length ratcheting. Without the need for externally controlled junction activation, our model is capable of generating spontaneous pulsing activities in tissues. |
Monday, March 6, 2023 4:12PM - 4:24PM |
D06.00005: Mechanical Basis for Epithelialization Christian Cammarota, Nicole Dawney, Mimi Jüng, Dan Bergstralh Epithelial tissues are comprised of sheets of cells that shape animal bodies. The architecture and mechanical integrity of epithelial tissues underlies their function. Our work addresses the question of how physical interactions, such as cell density, stiffness, and cell-cell or cell-substrate connections, affect the development of epithelial tissue architecture. The role played by physical interactions in architecture development is difficult to study in vivo since tissue development is predicated on the existence of physical cell connections. We developed a 2D computational model of epithelia in the plane perpendicular to most existing models of epithelia (such as vertex models), to investigate physical interactions in development. Our model simulates lateral cell surfaces as well as apical and basal tissue surfaces to investigate how physical interactions shape cell morphology. By using cell-cell border length as a readout, we find that a spatial constraint holding cells in proximity is required for the development of tissue architecture. We validated our in vitro predictions in experiments using cultured MDCK cells. Our work suggests that cell density is the primary factor in cell-cell border development and that cell-cell adhesion is subordinate. We are currently working to address the question of how physical constraints affect other epithelial processes. |
Monday, March 6, 2023 4:24PM - 4:36PM |
D06.00006: Vertex Modeling of Epithelial Tissues: Structural Changes from Out-of-plane Mechanics Sascha Hilgenfeldt, Mayisha Z Nakib, Jairo Martin Rojas Huamaní, William Brieher Vertex models of domain systems have been used to model and understand mechanical properties of the entire system as a function of not only physical parameters, but of structural signatures of the domains. In two dimensions, in particular, quantification of polygonal domain shapes, as well as the statistical distribution of domain areas and topologies (numbers of neighbors) provides important information about the rigidity and mechanical response of the system, which may represent a single-layer biological tissue such as an epithelium. |
Monday, March 6, 2023 4:36PM - 4:48PM |
D06.00007: Dynamic remodeling of fiber networks with stiff inclusions under compressive loading Bobby Carroll, Minh-Tri Ho Thanh, Alison E Patteson Tissue response to mechanical strain is important to biological processes like tissue development and maintenance; however, this relationship is not fully understood. Tissue mechanics are thought to be dominated by the extracellular matrix (ECM) consisting of a fibrous polymer network. However, these ECM polymer networks do not exhibit the compression stiffening response seen in real tissues. A model tissue system consisting of a fibrin network imbedded with inert stiff beads replicates this compression stiffening behavior. We employ bulk rheology and a custom imaging device to investigate the response of these fibrin-bead networks to uniaxial compression. The custom imaging device allows dynamic capture of network deformation at the mesoscale, a regime not previously well characterized. We find that the compression of fibrin-bead networks produces a series of remodeling processes, including the formation of a densified front, lateral stretching in the network, and fluid flow out the network. We argue the lateral network stretching is critical to the compression stiffening seen in these fibrin-bead networks. These findings are important to resolving challenges in tissue engineering at the intersection of physics, engineering, and medicine. |
Monday, March 6, 2023 4:48PM - 5:00PM |
D06.00008: Finite elasticity and interplay between curvature and rigidity in vertex models Arthur Hernandez, M Cristina Marchetti, Michael Moshe, Michael F Staddon Using a mean field approach, we study the finite mechanical response of the vertex model (VM) of biological tissue to compression and dilation and compare our analytical results to simulations. The VM is known to exhibit a transition between rigid and fluid-like or floppy states driven by geometric incompatibility: perimeter and area tension set a target shape, which may or may not be geometrically achievable and thereby engender frustration. We find that near the transition region the response to finite compression and dilation is asymmetric, with dilation yielding a higher bulk modulus. In the linear response regime where strains are arbitrarily small, the asymmetry only occurs at the transition point between solid and floppy states. The asymmetry can be understood as follows. Under compression, an initially solid VM can completely relax perimeter tension, and thereby reduce bulk and shear moduli. Conversely, an initially floppy VM can rigidify under dilation, thus increasing its bulk and shear moduli. These observations imply that re-scaling of cell area shifts the transition point between rigid and liquid states. Based on this insight, we calculate the re-scaling of cell area engendered by intrinsic curvature - namely local expansion (flat to saddle-like), and local compression (flat to spherical) - and obtain an analytical prediction for the rigidity transition in the presence of curvature. The predicted shift of the transition due to curvature is compared to simulation data from Ref. 1 and we find good agreement. Our analytical prediction of the rigidity transition for the VM on curved surfaces provides a new metric for predicting tissue rigidity from image data for curved tissues in a manner analogous to the flat case. |
Monday, March 6, 2023 5:00PM - 5:12PM |
D06.00009: Generating convergent-extension flows in a model epithelial tissue with active feedback Aondoyima Ioratim-Uba, Tanniemola B Liverpool, Silke Henkes Epithelial tissues undergo significant structural changes during development. An example is convergent-extension, which is observed during gastrulation and germ band extension. This involves tissue elongation in one direction, accompanied by narrowing in the perpendicular direction, mediated by active processes acting on mechanical or chemical tissue polarisation. However, we lack a mechanical understanding of how these changes occur. Here, we present a continuum model for an epithelial tissue with catch-bond type feedback for the actomyosin cortex, due to an anisotropic distribution of myosin molecular motors regulated by tension. We add this to a viscoelastic model tissue which is embedded in a background fluid that provides friction, inspired by physics of chick embryo gastrulation. Using an explicit numerical solution of the two-dimensional model, we find steady-state solutions with anomalous viscoelastic coefficients, as well as oscillations of the tissue that are triggered at sufficiently strong activity. We complement these findings with a linear response theory of this system, which shows that shear modes dominate the instability. |
Monday, March 6, 2023 5:12PM - 5:24PM |
D06.00010: T1 transitions as active hexatic defect annihilations Dimitrios Krommydas, Livio Nicola Carenza, Luca Giomi We show, analytically and numerically, that T1 transitions in epithelial tissue |
Monday, March 6, 2023 5:24PM - 5:36PM |
D06.00011: Compression Induced Fluidization in Vertex Models of Epithelial Tissues Avik B Mondal, David K Lubensky Vertex models are useful for simulating mechanics and collective behavior in confluent tissues. A notable feature of vertex models is a rigidity transition that occurs at zero cell motility. The transition can occur when the preferred perimeter of cells in the model drops below a threshold value, causing a large increase in junctional tensions and endowing the tissue with a finite yield stress. As a result, the rigidity transition is often described as occurring at a critical ratio of the preferred cell perimeter to the square root of the preferred area. In apparent contradiction to this conventional wisdom, a recent paper1 reported the striking finding that cell aggregates in the vertex model can fluidize under compression and used a mean field model to rationalize this observation. Here, we show that compression-induced fluidization is in fact an exact consequence of the most common vertex model free energy. We further explore numerically whether this phenomenon is robust to variations in the form of the free energy and comment on its implications for analysis of experimental data.
|
Monday, March 6, 2023 5:36PM - 5:48PM |
D06.00012: The role of collective cellular rearrangements in the rheology of dense biological tissues. Anh Q Nguyen, Dapeng(Max) Bi In many biological processes, a tissue's ability to deform and flow under shear shear is crucial for physiological function. Despite its importance to the understanding of embryonic development and tumor metastasis, the relationship between how a tissue flows plastically and cellular rearrangements is not well understood. Here, we use the vertex model to study the collective cell rearrangements and the tissue rheological response of a monolayer under external shear. We vary the adhesion and cortical tension of the cells to investigate the effect of this parameter on the tissue response to simple shear. We also construct a mean field model that is able to predict plasticity in experiment and simulations. |
Monday, March 6, 2023 5:48PM - 6:00PM |
D06.00013: Cell Dissociations in Collective Invasion Wei Wang, Robert A Law, Konstantinos Konstantopoulos, Brian A Camley Groups of eukaryotic cells can employ a collective migration strategy for efficiency in many biological processes, including wound healing and cancer invasion. However, confining environments met by cells during migration can lead to cell dissociations, e.g. cancer cells breaking off from an invading tumor front, leading to metastasis. What controls when cells dissociate, and whether they break off singly or in small groups? Can this be determined by cell-cell adhesion or chemotactic cues given to cells? We first design experiments to mimic cancer metastasis using microfluidic devices with microchannels of different widths. Most ruptures are single-cell ruptures, but we observe some ruptures of large groups (~20 cells) in wider channels. The rupture probability is nearly independent of channel width. To better understand the results, we propose a theoretical model with the phase field approach, and recapitulate the experimental results by introducing three different cell types (follower, guided, and a high-motility metabolically active subset of cells) based on their spatial position. These metabolic cells may explain why single-cell rupture is the universal most probable outcome. Our simulation results show that cell-channel adhesion is necessary for cells in narrow channels to invade, and strong cell-cell adhesion leads to fewer but larger ruptures. Chemotaxis also influences the rupture behavior: strong chemotaxis strength leads to larger and faster ruptures. We also study the relation between biological jamming transitions and cell dissociations. Our results suggest unjamming is necessary but not sufficient to create ruptures. |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700