SearcharxivSearch

arXiv subjects

B. Ladoux

Publications and source records attributed to B. Ladoux.

5 recordsLinked to original sources

Tissue stress measurements with Bayesian Inversion Stress Microscopy

Cells within biological tissue are constantly subjected to dynamic mechanical forces. Measuring the internal stress of tissues has proven crucial for our understanding of the role of mechanical forces in fundamental biological processes like morphogenesis, collective migration, cell division or cell elimination and death. Previously, we have introduced Bayesian Inversion Stress Microscopy (BISM), which is relying on measuring cell-generated traction forces in vitro and has proven particularly useful to measure absolute stresses in confined cell monolayers. We further demonstrate the applicability and robustness of BISM across various experimental settings with different boundary conditions, ranging from confined tissues of arbitrary shape to monolayers composed of different cell types. Importantly, BISM does not require assumptions on cell rheology. Therefore, it can be applied to complex heterogeneous tissues consisting of different cell types, as long as they can be grown on a flat substrate. Finally, we compare BISM to other common stress measurement techniques using a coherent experimental setup, followed by a discussion on its limitations and further perspectives.

q-bio.QM

A migrating epithelial monolayer flows like a Maxwell viscoelastic liquid

We perform a bidimensional Stokes experiment in an active cellular material: an autonomously migrating monolayer of Madin-Darby Canine Kidney (MDCK) epithelial cells flows around a circular obstacle within a long and narrow channel, involving an interplay between cell shape changes and neighbour rearrangements. Based on image analysis of tissue flow and coarse-grained cell anisotropy, we determine the tissue strain rate, cell deformation and rearrangement rate fields, which are spatially heterogeneous. We find that the cell deformation and rearrangement rate fields correlate strongly, which is compatible with a Maxwell viscoelastic liquid behaviour (and not with a Kelvin-Voigt viscoelastic solid behaviour). The value of the associated relaxation time is measured as $\tau = 70 \pm 15$~min, is observed to be independent of obstacle size and division rate, and is increased by inhibiting myosin activity. In this experiment, the monolayer behaves as a flowing material with a Weissenberg number close to one which shows that both elastic and viscous effects can have comparable contributions in the process of collective cell migration.

q-bio.TO

Kalman inversion stress microscopy

Although mechanical cues are crucial to tissue morphogenesis and development, the tissue mechanical stress field remains poorly characterized. Given traction force timelapse movies, as obtained by traction force microscopy of in vitro cellular sheets, we show that the tissue stress field can be estimated by Kalman filtering. After validation using numerical data, we apply Kalman inversion stress microscopy to experimental data. We combine the inferred stress field with velocity and cell shape measurements to quantify the rheology of epithelial cell monolayers in physiological conditions, found to be close to that of an elastic and active material.

q-bio.QM

Collective cell migration without proliferation: density determines cell velocity and wave velocity

Collective cell migration contributes to embryogenesis, wound healing and tumor metastasis. Cell monolayer migration experiments help understanding what determines the movement of cells far from the leading edge. Inhibiting cell proliferation limits cell density increase and prevents jamming; we observe long-duration migration and quantify space-time characteristics of the velocity profile over large length- and time-scales. Velocity waves propagate backwards and their frequency depends only on cell density at the moving front. Both cell average velocity and wave velocity increase linearly with the cell effective radius regardless of the distance to the front. Inhibiting lamellipodia decreases cell velocity while waves either disappear or have a lower frequency. Our model combines conservation laws, monolayer mechanical properties and a phenomenological coupling between strain and polarity: advancing cells pull on their followers which then become polarized. With reasonable values of parameters, this model agrees with several of our experimental observations. Together, our experiments and model disantangle the respective contributions of active velocity and of proliferation in monolayer migration, explain how cells maintain their polarity far from the moving front, and highlight the importance of strain-polarity coupling and density in long-range information propagation.

physics.bio-ph

Inference of internal stress in a cell monolayer

We combine traction force data with Bayesian inversion to obtain an absolute estimate of the internal stress field of a cell monolayer. The method, Bayesian inversion stress microscopy (BISM), is validated using numerical simulations performed in a wide range of conditions. It is robust to changes in each ingredient of the underlying statistical model. Importantly, its accuracy does not depend on the rheology of the tissue. We apply BISM to experimental traction force data measured in a narrow ring of cohesive epithelial cells, and check that the inferred stress field coincides with that obtained by direct spatial integration of the traction force data in this quasi-one-dimensional geometry.

q-bio.QM