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Introduction
Additional affiliations
February 2019 - present
October 2015 - September 2018
December 2014 - September 2015
Publications
Publications (44)
We study the deformation and the remodeling of two-dimensional cellular materials. Examples are epithelia, which undergo large-scale deformations during the development of a multi-cellular organism. Such large-scale deformations emerge from processes such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. In this artic...
Morphogenesis of an epithelial tissue emerges from the behavior of its constituent cells, including changes in shape, rearrangements, and divisions. In many instances the directionality of these cellular events is controlled by the polarized distribution of specific molecular components. In recent years, our understanding of morphogenesis and polar...
Background:
The conserved Fat and Core planar cell polarity (PCP) pathways work together to specify tissue-wide orientation of hairs and ridges in the Drosophila wing. Their components form intracellularly polarized complexes at adherens junctions that couple the polarity of adjacent cells and form global patterns. How Fat and Core PCP systems int...
Athermal (i.e. zero-temperature) under-constrained systems are typically floppy, but they can be rigidified by the application of external strain, which is theoretically well understood. Here and in the companion paper, we extend this theory to finite temperatures for a very broad class of under-constrained systems. In the vicinity of the athermal...
Athermal (i.e. zero-temperature) under-constrained systems are typically floppy, but they can be rigidified by the application of external strain. Following our recently-developed analytical theory for the athermal limit, here and in the companion paper, we extend this theory to under-constrained systems at finite temperatures close to the athermal...
Biological cells can actively tune their intracellular architecture according to their overall shape. Here we explore the rheological implication of such coupling in a minimal model of a dense cellular material where each cell exerts an active mechanical stress along its axis of elongation. Increasing the active stress
amplitude leads to several tr...
Tissue flow during morphogenesis is commonly driven by local constriction of cell cortices, which is caused by the activation of actomyosin contractility. This can lead to long-range flows due to tissue viscosity. However, in the absence of cell-intrinsic polarized forces or polarity in forces external to the tissue, these flows must be symmetric a...
Active matter with local polar or nematic order is subject to the well-known Simha-Ramaswamy instability. It is so far unclear how, despite this instability, biological tissues can undergo robust active anisotropic deformation during animal morphogenesis. Here we show that protein concentration gradients (e.g. morphogen gradients), which are known...
Tissue flow during morphogenesis is commonly driven by local constriction of cell cortices, which is caused by activation of actomyosin contractility. This can lead to long-range flows due to tissue viscosity. However, in the absence of cell-intrinsic polarized forces or polarity in forces external to the tissue, these flows must be symmetric and c...
Disordered spring networks are a useful paradigm to examine macroscopic mechanical properties of amorphous materials. Here, we study the elastic behavior of under-constrained spring networks, i.e. networks with more degrees of freedom than springs. While such networks are usually floppy, they can be rigidified by applying external strain. Recently,...
Active matter with local polar or nematic order is subject to the well-known Simha-Ramaswamy instability. It is so far unclear how, despite this instability, biological tissues can undergo robust active anisotropic deformation during animal morphogenesis. Here we discuss whether protein concentration gradients (e.g. morphogen gradients), which are...
Biological cells can actively tune their intracellular architecture according to their overall shape. Here we explore the rheological implication of such coupling in a minimal model of a dense cellular material where each cell exerts an active mechanical stress along its axis of elongation. Increasing the active stress amplitude leads to several tr...
Phase separation can drive spatial organization of multicomponent mixtures. For instance in developing animal embryos, effective phase separation descriptions have been used to account for the spatial organization of different tissue types. Similarly, separation of different tissue types is also observed in stem cell aggregates, where the emergence...
abstractVertex models describe biological tissues as tilings of polygons. In standard vertex models, the tissue dynamics result from a balance between isotropic stresses, which are associated with the bulk of the cells, and tensions associated with cell–cell interfaces. However, in this framework it is less obvious how to describe anisotropic stres...
Disordered spring networks are a useful paradigm to examine the relation between microscopic material structure and macroscopic mechanical properties of amorphous materials. Here, we study the elastic behavior of under-constrained spring networks, i.e. networks with more degrees of freedom than springs. While such networks are usually floppy, they...
Phase separation can drive spatial organization of multicomponent mixtures. For instance in developing animal embryos, effective phase separation descriptions have been used to account for the spatial organization of different tissue types. Similarly, separation of different tissue types and the emergence of a polar organization is also observed in...
Tissue, cell, and nucleus morphology change during tumor progression. In 2D confluent cell cultures, different tissue states, such as fluid (unjammed) and solid (jammed), are correlated with cell shapes. These results do not have to apply a priori to three dimensions. Cancer cell motility requires and corresponds to a fluidization of the tumor tiss...
Within developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, e...
Within developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, e...
Within developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, e...
Significance
What do a guitar string and a balloon have in common? They are both floppy unless rigidified by geometric incompatibility. The same kind of rigidity transition in underconstrained materials has more recently been discussed in the context of disordered biopolymer networks and models for biological tissues. Here, we propose a general app...
We present a novel approach to understanding prestress-induced rigidity in under-constrained materials, including sub-isostatic 2D spring networks and 2D and 3D vertex models for dense biological tissues. We show that in all these models a purely geometric criterion, represented by a minimal length $\bar\ell_\mathrm{min}$, determines the onset of r...
Vertex models are a popular approach to simulating the mechanical and dynamical properties of dense biological tissues, describing the tissue as a network of polygons. Recently a class of two-dimensional vertex models was shown to exhibit a disordered rigidity transition controlled by the preferred cellular geometry, which was subsequently echoed b...
Although cell shape can reflect the mechanical and biochemical properties of the cell and its environment, quantification of 3D cell shapes within 3D tissues can be difficult, typically requiring digital reconstruction from a stack of 2D images. We investigate a simple alternative technique that can provide information about the 3D shapes of cells...
The origin of rigidity in disordered materials is an outstanding open problem in statistical physics. Previously, a class of 2D cellular models has been shown to undergo a rigidity transition controlled by a mechanical parameter that specifies cell shapes. Here, we generalize this model to 3D and find a rigidity transition that is similarly control...
How epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer's vesicle (KV), a transient organ with a fluid-filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3-dim...
Statistical power analysis for the non-significant AP cell volume and LWR differences in Figure 6A–C.
Here, we show the false negative rate β that results from testing against the alternative hypothesis that the true AP difference in a given case was the same as for the MO control at 8 ss (Figure 6A). The statistical power in each case is 1-β.
Statistical power analysis for the non-significant AP cell volume and LWR differences in Figure 3A–D.
Here, we show the false negative rate β that results from testing against the alternative hypothesis that the true AP difference in a given case was the same as for the DMSO control at 8ss (Figure 3A). The statistical power in each case is 1-β.
Percentage differences of cell volume, cell cross sectional area, and cell height between anterior and posterior cells [(Post – Ant)/Post] at 2 ss and 8 ss for DMSO control embryos.
The cell volume is proportional to the product of cross-sectional area and height. As a consequence, if the AP difference in cell volume was fully due to the difference...
Preferred areas A0 prescribed in our vertex model simulations for the different cell types at 2 ss and 8 ss.
The listed values for lumen and KV cells are experimentally measured average cross-sectional areas from DMSO-treated control embryos. The 2 ss values for the external cells were set to the average of KV-ant and KV-post cells. The preferred a...
How epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer’s vesicle (KV), a transient organ with a fluid-filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3-dim...
Vertex models are a popular approach to modeling the mechanical and dynamical properties of dense biological tissues, describing the tissue as a network of connected polygons representing the cells. Recently a class of two-dimensional vertex models was shown to exhibit a disordered rigidity transition controlled by the preferred cellular geometry,...
Significance
Using a self-propelled Voronoi model of epithelia known to predict a liquid–solid transition, we examine the interplay between cell motility and cell shape, tuned by cortex contractility and cell–cell adhesion, in controlling the mechanical properties of tissue. Our work provides a unifying framework for existing, seemingly distinct no...
We present a hydrodynamic theory to describe shear flows in developing epithelial tissues. We introduce hydrodynamic fields corresponding to state properties of constituent cells as well as a contribution to overall tissue shear flow due to rearrangements in cell network topology. We then construct a generic linear constitutive equation for the she...
In multi-cellular organisms, morphogenesis translates processes at the cellular scale into tissue deformation at the scale of organs and organisms. To understand how biochemical signaling regulates tissue form and function, we must understand the mechanical forces that shape cells and tissues. Recent progress in developing mechanical models for tis...
We propose a hydrodynamic theory to describe shear flows in developing epithelial tissues. We introduce hydrodynamic fields corresponding to state properties of constituent cells as well as a contribution to overall tissue shear flow due to rearrangements in cell network topology. We then construct a constitutive equation for the shear rate due to...
Segmentation and tracking of cells in long-term time-lapse experiments has emerged as a powerful method to understand how tissue shape changes emerge from the complex choreography of constituent cells. However, methods to store and interrogate the large datasets produced by these experiments are not widely available. Furthermore, recently developed...
How tissue shape emerges from the collective mechanical properties and behavior of individual cells is not understood. We combine experiment and theory to study this problem in the developing wing epithelium of Drosophila. At pupal stages, the wing-hinge contraction contributes to anisotropic tissue flows that reshape the wing blade. Here, we quant...
Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing
How tissue shape emerges from the collective mechanical properties and behavior of individual cells is not understood. We combine experiment and theory to study this problem in the developing wing epithelium of Drosophila. At pupal stages, the wing-hinge contraction contributes to anisotropic tissue flows that reshape the wing blade. Here, we quant...
Epithelial tissues develop planar polarity that is reflected in the global alignment of hairs and cilia with respect to the tissue axes. The planar cell polarity (PCP) proteins form asymmetric and polarized domains across epithelial junctions that are aligned locally between cells and orient these external structures. Although feedback mechanisms c...
In this paper, we analytically examine the influence of synaptic short-term plasticity (STP) on the transfer of rate-coded information through synapses. STP endows each presynaptic input spike with an amplitude that depends on previous input spikes. We develop a method to calculate the spectral statistics of this amplitude modulated spike train (po...
