Generating active T1 transitions through mechanochemical feedback

  1. Rastko Sknepnek  Is a corresponding author
  2. Ilyas Djafer-Cherif
  3. Manli Chuai
  4. Cornelis Weijer  Is a corresponding author
  5. Silke Henkes  Is a corresponding author
  1. School of Science and Engineering, University of Dundee, United Kingdom
  2. School of Life Sciences, University of Dundee, United Kingdom
  3. School of Mathematics, University of Bristol, United Kingdom
  4. Leiden Institute of Physics, Leiden University, Netherlands
8 figures, 2 tables and 1 additional file

Figures

Figure 1 with 2 supplements
An active junction.

(A) An external pulling force of magnitude Text induces tension T in a cell–cell junction of length l, which consists of passive viscoelastic and active components. The passive component consists of …

Figure 1—figure supplement 1
Key ingredients of the single active junction model.

(A) The junction is modelled as a Maxwell element with stiffness k and viscosity η (and the relaxation timescale τv=η/k) connected in parallel with the active forcing, and an elastic barrier with …

Figure 1—figure supplement 2
A linear chain of active junctions.

(A) Schematic of a linear chain for viscoelastic junctions with active tension feedback. The chain is formed by connecting in series the active viscoelastic elements shown in Figure 1—figure …

Figure 2 with 14 supplements
An active T1 transition event.

(A) Top panel: the mechanical anisotropy in the initial state is produced by applying pulling forces (green arrows) in the horizontal direction to the left and right boundaries. Bottom panel: the …

Figure 2—figure supplement 1
Schematic representation of the key ingredients in the vertex model with active junctions.

(A) The total force on vertex i can be expressed as a sum of forces due to junctions. For the junction e, Ce,l and Ce,r are the cells to the left and the right, respectively, when looking in the …

Figure 2—video 1
Simulation of a passive system with applied horizontal pulling for fpull=0.15f*.

Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark grey), buffer (intermediate grey), passive (light grey). In this video activity is …

Figure 2—video 2
Low activity system with no T1 transitions.

Activity is set to β=0.4f* for the four central cells and the patch is pulled horizontally with fpull=0.15f*, τm=100t*, and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured …

Figure 2—video 3
Active T1 transition.

Activity is set to β=0.8f* for the four central cells and the patch is pulled horizontally with fpull=0.15f*, τm=100t*, and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured …

Figure 2—video 4
System with low pulling force.

Activity is set to β=0.8f* for the four central cells and the patch is pulled horizontally with fpull=0.05f*, τm=100t*, and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured …

Figure 2—video 5
System with too high pulling force.

Activity is set to β=0.8f* for the four central cells and the patch is pulled horizontally with fpull=0.25f*, τm=100t*, and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured …

Figure 2—video 6
System with too high activity.

Activity is set to β=1.2f* for the four central cells and the patch is pulled horizontally with fpull=0.15f*, τm=100t*, and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured …

Figure 2—video 7
Active T1 transition with low τm and τv.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=20t* and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 8
Active T1 transition with low τm.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=20t* and τv=100t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 9
Active T1 transition with low τv.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=100t* and τv=20t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 10
Active T1 transition at intermediate values of τm and τv.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=100t* and τv=100t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 11
Active T1 transition at high τv.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=100t* and τv=500t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 12
Active T1 transition at high τm.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=500t* and τv=100t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 2—video 13
Active T1 transition at high τm and τv.

Activity is set to β=1.0f* and the patch is pulled horizontally with fpull=0.15f* with τm=500t* and τv=500t*. Left panel - junction and cell myosin; right panel - junction tension, cells are coloured by type, active (dark …

Figure 3 with 1 supplement
Junction dynamics during the active T1 transition shown in Figure 2.

(A) Definition of central (red/blue – junction that disappears/appears), inner (orange), and outer (blue-green) shoulder junctions through the T1 transition. (B) Central junction: myosin, m (green; …

Figure 3—figure supplement 1
Continuous strain tensors through the active T1 transition, for β=0.8f*, fpull=0.15f*, and the other parameters corresponding to Figure 2 and Figure 3.

(A) Statistical strain tensor U^ defined in Equation 20, with the initial undeformed state used as reference configuration. (B) Total strain, that is, integrated V^ tensor defined in Equation 24. (C)…

Existence and timescales of T1 transitions in the vertex model with active junctions as a function of fpull and β, averaged over n=32 simulations with different realisations of the myosin noise.

(A) Probability of a central T1 transition. The red line is the 50% probability contour of any T1 occurring in the simulation. (B) Typical timescale for the T1 transition to occur, measured as the …

Robustness of the T1 mechanism as a function of τv and τm for β=1.0f* and fpull=0.15f*.

(A) Probability of a central T1 event, averaged over n=32 simulations with different realisations of the myosin noise. The probability of any T1 event is 1 throughout. (B) Contraction time to collapse …

Figure 6 with 2 supplements
Disordered active tissue at time t700t* as a function of the magnitude of the pulling force fpull and activity β.

The region of convergence–extension is at the centre of the diagram, around β0.4-0.6f* and fpull0.1-0.3f*. The remaining parameters are the same as in Figure 2.

Figure 6—video 1
Video of simulations of active contractions in disordered tissues for a range of activities, β, and magnitudes of the pulling force, fpull.

The system is first stretched for t=150t with activity switched off. During the initial stretching period, myosin is allowed to build anisotropy, but it does not feed back onto tension. This results in …

Figure 6—video 2
Active T1 transitons in a random patch.

Activity is set to β=0.5f* and the patch is pulled horizontally with fpull=0.2f* with τm=100t and τv=20t. Left panel - junction and cell myosin; right panel - junction tension, and all cells are active.

Figure 7 with 3 supplements
Characterisation of convergence-extension in a random tissue patch.

(A) Snapshot of a random tissue patch for β=0.5f* and fpull=0.2f* at t700t*,that is during the convergence–extension flow. Red arrow indicates that a constant pulling force is applied throughout the entire …

Figure 7—figure supplement 1
Continuous strain tensors for the fully active tissue at β=0.5f*, fpull=0.2f*, and the other parameters corresponding to Figure 2 and Figure 3.

(A) Statistical strain tensor U^ defined in Equation 20, with the initial undeformed state used as reference configuration. (B) Total strain, that is, integrated V^ tensor defined in Equation 24. (C)…

Figure 7—figure supplement 2
Measuring T1 transitions in the fully active random patch.

A representative example taken from a sample of n=5 simulations for β=0.5f*, fpull=0.2f*. (A) Appearing and disappearing junctions as a function of simulation frame number and angle, before filtering. Inset: raw …

Figure 7—figure supplement 3
T1 histograms in the parameter range where no convergence–extension occurs.

(A) Passive tissue at β=0 pulled with fpull=0.2f*, T1s are passive and aligned along pulling direction. (B) Active tissue at β=0.5f* with no applied force fpull=0.0f*, here T1s are distributed isotropically. (C) …

Figure 8 with 3 supplements
Analysis of the tissue flows in the early-stage chick embryo.

(A) Image of a typical early-stage chick embryo prior to the gastrulation (i.e. primitive streak formation). The primitive streak will form along the yellow dashed line. The direction of myosin …

Figure 8—figure supplement 1
Region of interest in the anterior of the embryo.

(A) Integrated total strain ε^tot(t) and (B) elastic strain U^(t).

Figure 8—video 1
Image sequence taken at the base of the forming streak showing cell intercalations.

Centres of some cells are labelled with coloured dots for easier identification. Crossed blue and red lines indicate individual intercalation events. Blue lines indicate the direction of junction …

Figure 8—video 2
Image sequence taken in the region of epiblast in front of forming streak.

Centres of some cells are labelled with coloured dots for easier identification. Crossed blue and red lines indicate individual intercalation events. Blue lines indicate the direction of junction …

Tables

Table 1
Values of the parameters in the single-junction model.

Units: length (a), time (t*=ζ/k), force (ka).

Base
ParameterDescription
kSpring constant
aBarrier rest length
ζFriction with substrate
Model
ParameterDescriptionValue range
BBarrier spring constant0-0.2k
TextApplied external tension0-1ka
βMyosin activity0-3ka
τvViscoelastic time10t*
τmMyosin time10t*
m0Myosin reference level0.5
T*Threshold tension0.3ka
k0Slope of m vs. T at T2/T*
αTension-independent myosin dissociation1
Table 2
Values of the parameters used in the vertex model with active junctions.

Units: length (a), time (t*=ζ/(Γ+k)), force (f*=(Γ+k)a).

Base
ParameterDescription
aHexagonal cell edge length
ΓPerimeter modulus
kSpring constant
ζFriction with substrate
Model
ParameterDescriptionValue range
κArea modulus1f*/a3
A0Target cell area33a2/2
P0Target cell perimeter6a
fpullPulling force0.0-0.3f*
βMyosin activity0.0-1.4f*
τvViscoelastic time100-103t*
τmMyosin time101-103t*
T*Threshold tension0.3f*
K0Slope of m vs. T at T2/T*
m0Myosin reference level0.5
MTotal cell myosin6
fVariance of myosin fluctuations1
αTension-independent myosin dissociation0.1

Additional files

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