Biology subjects

Mani, M.

Publications and source records attributed to Mani, M..

7 recordsLinked to original sources

bioRxiv2018

QuBiT: A quantitative tool for epithelial tubes reveals cell dynamics and unexpected patterns of organization during Drosophila tracheal morphogenesis

Biological tubes are essential for animal survival, and their functions are critically dependent on tube shape. Analyzing the contributions of cell shape and organization to the morphogenesis of small tubes has been hampered by the limitations of existing programs in quantifying cell geometry on highly curved tubular surfaces and calculating tube-specific parameters. We therefore developed QuBiT (Quantitative Tool for Biological Tubes) and used it to analyze morphogenesis during embryonic Drosophila tracheal (airway) development. We find that there are previously unknown anterior-to-posterior (A-P) gradients of cell orientation and aspect ratio, and that there is periodicity in the organization of cells in the main tube. Furthermore, cell intercalation during development dampens an A-P gradient of the number of the number of cells per cross-section of the tube, but these intercalation events do not change the patterns of cell connectivity. These unexpected findings demonstrate the importance of a computational tool for analyzing the morphogenesis of small diameter biological tubes.

cell biology↗

bioRxiv2018

The Role of Cytoplasmic Interactions in the Collective Polarization of Tissues and its Interplay with Cellular Geometry

Planar cell polarity (PCP), the ability of a tissue to polarize coherently over multicellular length scales, provides the directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intra-cellular and intercellular mechanisms, how they couple together to produce the collective response remains an active area of investigation. Exploring a phenomeno-logical reaction-diffusion model, we predict a crucial, and novel, role for cytoplasmic interactions in the large-scale correlations of cell polarities. We demonstrate that finite-range (i.e. nonlocal) cytoplasmic interactions are necessary and sufficient for the robust and long-range polarization of tissues -- even in the absence of global cues -- and are essential to the faithful detection of weak directional signals. Strikingly, our model re-capitulates an observed influence of anisotropic tissue geometries on the orientation of polarity. In order to facilitate a conversation between theory and experiments, we compare five distinct classes of in silico mutants with experimental observations. Within this context, we propose quantitative measures that can guide the search for the participant molecular components, and the identification of their roles in the collective polarization of tissues.

biophysics↗

bioRxiv2018

A mechanism for the proliferative control of tissue mechanics in the absence of growth

During the development of a multicellular organism, cells coordinate their activities to generate mechanical forces, which in turn drives tissue deformation and eventually defines the shape of the adult tissue. Broadly speaking, it is recognized that mechanical forces can be generated through differential growth and the activity of the cytoskeleton. Based on quantitative analyses of live imaging of the Drosophila dorsal thorax, we suggest a novel mechanism that can generate contractile forces within the plane of an epithelia - via cell proliferation in the absence of growth. Utilizing force inference techniques, we demonstrate that it is not the gradient of junction tension but the divergence of junction-tension associated stresses that induces the area constriction of the proliferating tissue. Using the vertex model simulations, we show that the local averaged stresses can be roughly elevated by a fold of p 2 per cell division without growth. Moreover, this mechanism is robust to disordered cell shapes and the division anisotropy, but can be dominated by growth. In competition with growth, we identify the parameter regime where this mechanism is effective and suggest experiments to test this new mechanism.

developmental biology↗

bioRxiv2018

Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

During epithelial morphogenesis, cell contacts (junctions) are constantly remodeled by mechanical forces that work against adhesive forces. E-cadherin complexes play a pivotal role in this process by providing persistent cell adhesion and by transmitting mechanical tension. In this context, it is unclear how mechanical forces affect E-cadherin adhesion and junction dynamics.\n\nDuring Drosophila embryo axis elongation, Myosin-II activity in the apico-medial and junctional cortex generates mechanical forces to drive junction remodeling. Here we report that the ratio between Vinculin and E-cadherin intensities acts as a ratiometric readout for these mechanical forces (load) at E-cadherin complexes. Medial Myosin-II loads E-cadherin complexes on all junctions, exerts tensile forces, and increases levels of E-cadherin. Junctional Myosin-II, on the other hand, biases the distribution of load between junctions of the same cell, exerts shear forces, and decreases the levels of E-cadherin. This work suggests distinct effects of tensile versus shear stresses on E-cadherin adhesion.

cell biology↗

bioRxiv2017

A jump distance based parameter inference scheme for particulate trajectories in biological settings

One type of biological data that needs more quantitative analytical tools is particulate trajectories. This type of data appears in many different contexts and across scales in biology: from the trajectory of bacteria performing chemotaxis to the mobility of ms2 spots within nuclei. Presently, most analyses performed on data of this nature has been limited to mean square displacement (MSD) analyses. While simple, MSD analysis has several pitfalls, including difficulty in selecting between competing models, handling systems with multiple distinct sub-populations, and parameter extraction from limited time-series data. Here, we provide an alternative to MSD analysis using the jump distance distribution (JDD). The JDD resolves several issues: one can select between competing models of motion, have composite models that allow for multiple populations, and have improved error bounds on parameter estimates when data is limited. A major consequence is that you can perform analyses using a fraction of the data required to get similar results using MSD analyses, thereby giving access to a larger range of temporal dynamics when the underlying stochastic process is not stationary. In this paper, we construct and validate a derivation of the JDD for different transport models, explore the dependence on dimensionality of the process, and implement a parameter estimation and model selection scheme. We demonstrate the power of this scheme through an analysis of bacterial chemotaxis data, highlighting the interpretation of results and improvements upon MSD analysis. We expect that our proposed scheme provides quantitative insights into a broad spectrum of biological phenomena requiring analysis of particulate trajectories.

biophysics↗

bioRxiv2017

A scheme for 3-dimensional morphological reconstruction and force inference in the early C. elegans embryo

In this study, we present novel schemes for the reconstruction of cellular morphology and the inference of forces in the early C. elegans embryo. We have developed and bench-marked a morphological reconstruction scheme that transforms live-imaging of cellular membranes into a point cloud of smoothed surface patches, which facilitates accurate estimation of membrane curvatures and the angles between membranes.\n\nAssuming an isotropic and homogeneous distribution of tensions along a membrane, we infer a pattern of forces that are 7% deviated from force balance at edges, and 10% deviated from the Young-Laplace relation at membrane faces. We have also demonstrated the stability of our scheme by sensitivity analysis of the coefficient matrices involved and the reproducibility of our image-analysis and force inference pipeline.

biophysics↗

bioRxiv2017

Matrix Production In Bacillus subtilis Biofilms Is Localized To A Propagating Front

Bacterial biofilms are surface attached microbial communities encased in self-produced extracellular polymeric substances (EPS). Development of a mature biofilm must require coordinating cell differentiation and multicellular activity at scales much larger than the single microbial unit. Here we demonstrate that during development of Bacillus subtilis biofilms, EPS matrix production is localized to a front propagating at the periphery. We show that within the front, cells switch off matrix production and transition to sporulation after a set time delay of[~] 100 min. Correlation analyses of fluctuations in fluorescence reporter activity reveals that the front emerges from a pair of gene expression waves of matrix production and sporulation. The expression waves travel across cells that are immobilized in the biofilm matrix, in contrast to active cell migration or horizontal colony spreading. A single length scale and time scale couples the spatiotemporal propagation of both fronts throughout development, with the front displacement obeying a t1/2 scaling law. As a result, gene expression patterns within the advancing fronts collapse to self-similar expression profiles. Our results indicate that development of bacterial biofilms may be governed by universal wave-like dynamics localized to a self-similar front.

biophysics↗