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Biology subjects

Yeomans, J. M.

Publications and source records attributed to Yeomans, J. M..

4 recordsLinked to original sources

Quantitative multi-scale morphodynamic analysis reveals ratchet-like collective DVE migration and epiblast retrograde cell flow during anterior patterning in the mouse embryo

The collective unidirectional migration of distal visceral endoderm (DVE) cells in the early mouse embryo is required to pattern the anterior-posterior (A-P) axis in the epiblast. It is unknown to what extent A-P axial asymmetries exist prior to DVE migration, how migration becomes channeled towards one side of the embryo, and whether the epiblast cells they migrate over have coordinated movements. We developed a quantitative embryo-wide, tissue-tracking approach to analyse visceral endoderm and epiblast tissue morphodynamics in a longitudinal light-sheet imaged, multi-embryo data-set. Here we show that asymmetric morphology of the ectoplacental cone already present prior to DVE migration correlates with the alignment of the A-P axis but not its polarity. DVE cell movements are initiated with a relatively low cell coordination and small net migration, then get channelled in an abrupt transition to a highly coordinated, uni-directional anterior motion. This anteriorwards migration is characterised by a ratchet-like, intermittent motion. Vertex modelling demonstrates that tissue rheology can account for DVE start-stop motion, and suggests that T1-mediated stress relaxation in the surrounding tissue can facilitate intermittent DVE motion without requiring intrinsic fluctuations in DVE velocity. Finally, comparing cell movement of the DVE with the underlying epiblast reveals a previously unknown coordinated motion in the anterior epiblast, opposite to the direction of DVE migration. Together these data provide insights into the origin of embryonic axial asymmetry and a previously unappreciated coordination between VE and epiblast tissue-motion during anterior-posterior patterning. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/720339v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1cfe4fdorg.highwire.dtl.DTLVardef@1c2c3e6org.highwire.dtl.DTLVardef@1cb6a5corg.highwire.dtl.DTLVardef@1b3ed19_HPS_FORMAT_FIGEXP M_FIG C_FIG See supplemental movie: animated abstract

developmental biology↗

Self organisation of invasive breast cancer driven by the interplay of active and passive nematic dynamics

In invasive breast cancer, cell clusters of varying sizes and shapes are embedded in the fibrous extracellular matrix (ECM). Although the prevailing view attributes this structure to increasing disorder resulting from loss of function and dedifferentiation, our findings reveal that it arises through a process of active self-organization driven by cancer cell motility. Simulations and histological analyses of tumours from over 2,000 breast cancer patients reveal that motile, aligned cancer cells within clusters move as active nematic aggregates through the surrounding highly aligned ECM fibres, which form a confining, passive nematic phase. Cellular motion leads to cluster splitting and coalescence. The degree of cluster activity, combined with heterogeneity in cell motility, is reflected in specific scaling behaviours for cluster shape, size distribution, and the distance between cluster boundaries and nematic defects in ECM alignment. Increased activity estimates correlate with tumour progression and are associated with a poorer prognosis for patients.

biophysics↗

Active forces in confluent cell monolayers

We use a computational phase-field model together with analytical analysis to study how inter-cellular active forces can mediate individual cell morphology and collective motion in a confluent cell monolayer. Contractile inter-cellular interactions lead to cell elongation, nematic ordering and active turbulence, characterised by motile topological defects. Extensile interactions result in frustration, and perpendicular cell orientations become more prevalent. Furthermore, we show that contractile behaviour can change to extensile behaviour if anisotropic fluctuations in cell shape are considered.

biophysics↗

Activity pulses induce spontaneous flow reversals in viscoelastic environments

Complex interactions between cellular systems and their surrounding extracellular matrices are emerging as important mechanical regulators of cell functions such as proliferation, motility, and cell death, and such cellular systems are often characterized by pulsating acto-myosin activities. Here, using an active gel model, we numerically explore the spontaneous flow generation by activity pulses in the presence of a viscoelastic medium. The results show that cross-talk between the activity-induced deformations of the viscoelastic surroundings with the time-dependent response of the active medium to these deformations can lead to the reversal of spontaneously generated active flows. We explain the mechanism behind this phenomenon based on the interaction between the active flow and the viscoelastic medium. We show the importance of relaxation timescales of both the polymers and the active particles and provide a phase-space over which such spontaneous flow reversals can be observed. Our results suggest new experiments investigating the role of controlled pulses of activity in living systems ensnared in complex mircoenvironments.

biophysics↗