Adhesion, which includes cell-to- cell and cell-to-extracellular- matrix adhesion, plays an important role in cancer invasion and metastasis. These processes require interactions and signalling cross-talks between proteins and cellular components occurring at different temporal and spatial scales. Interactions between human mammary epithelial cells and movement on a two- dimensional surface. Taken from: http://www.youtube.com/user/YamadaLab (1) Liu et al (2010), PNAS, doi:10.1073/pnas.0914547107 (2) Heinrich et al (2008), Cell Adhesion & Migration, 2(2): 58–68 (3) Cavalcanti-Adam et al (2007), Biophys J, 92: 2964–2974 Cell-cell adhesive interaction studies: time series plots of traction and tugging forces between two endothelial cells (1) Cell-matrix adhesive interaction studies: fluctuations in the area of cell-substrate contact on (A) a non-adhesive, (B) a hydrophilic, and (C) a hydrophobic surface (2) Highly dynamic cycles of protrusion and retractions of a cell adhering to different kind of surfaces (3) (4) Ramis-Conde et al. (2008) Biophys J, 95:155–165 (5) Andasari et al. (2012) PLOs ONE, 7(3): e33726 Intracellular dynamics of the interactions of the cell-cell adhesion components. Fluctuations due to the nature of the GGH model (5) • Multiscale individual-cell based modelling approach combining intracellular and cellular levels • Lattice-based technique: GGH model • Cell detachment model based on intracellular dynamics of the interactions of the main cell- cell adhesion components: * E-cadherin * β-catenin Simulation results using CompuCell3D, a GGH model’s simulation environment (5) ODE model of the cell-cell adhesion components (4) A schematic diagram of the E-cadherin and interactions with β-catenin (5) Cell-matrix interactions based on intracellular dynamics of the main cell- matrix adhesion components (6) : * cell surface receptor: integrin * matrix glycoprotein: fibronectin * actin cytoskeleton Cell-matrix adhesion simulations using CompuCell3D Adhesion force comparison between experimental data (left) and model (right) (6) (6) Andasari and Chaplain (2012), MMNP, 7(1): 29–48 3D platform 2D platform • Cell-matrix attachment and detachment model at cell front and rear, respectively, for migrating cells • Incorporate stochastic aspects for the intracellular dynamics in the cell-cell and cell-matrix adhesion models • Combine the cell-cell and cell-matrix adhesion models use Src as an intermediate between E-cadherin (cell-cell adhesion) and integrin (cell-matrix adhesion)? • Is polarization needed? Stroma cells Detached & migrated cells Tumour Stroma cells Migrated cell This model is for cell-matrix attachment at cell front

This model is for cell-matrix attachment at cell frontpeople.bu.edu/andasari/files/PosterCMMB2012.pdf · Adhesion, which includes cell-to-cell and cell-to-extracellular-matrix adhesion,

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Page 1: This model is for cell-matrix attachment at cell frontpeople.bu.edu/andasari/files/PosterCMMB2012.pdf · Adhesion, which includes cell-to-cell and cell-to-extracellular-matrix adhesion,

Interactions between human mammary epithelial cells and movement on a two-

dimensional surface. Taken from:http://www.youtube.com/user/YamadaLab

(1) Liu et al (2010), PNAS, doi:10.1073/pnas.0914547107(2) Heinrich et al (2008), Cell Adhesion & Migration, 2(2): 58–68(3) Cavalcanti-Adam et al (2007), Biophys J, 92: 2964–2974

Cell-cell adhesive interaction studies: time series plots of traction and tugging forces between two

endothelial cells(1)

Cell-matrix adhesive interaction studies: fluctuations in the area of cell-substrate contact on (A) a non-adhesive, (B) a

hydrophilic, and (C) a hydrophobic surface(2)

Highly dynamic cycles of protrusion and retractions of a cell adhering to different

kind of surfaces(3)

(4) Ramis-Conde et al. (2008) Biophys J, 95:155–165(5) Andasari et al. (2012) PLOs ONE, 7(3): e33726

Intracellular dynamics of the interactions of the cell-cell adhesion components. Fluctuations due to the

nature of the GGH model(5)

• Multiscale individual-cell based modelling approach combining intracellular and cellular levels

• Lattice-based technique: GGH model• Cell detachment model based on intracellular

dynamics of the interactions of the main cell-cell adhesion components:

* E-cadherin* β-catenin

Simulation results using CompuCell3D, a GGH model’s simulation environment(5)

ODE model of the cell-cell adhesion components(4)

A schematic diagram of the E-cadherin and interactions with

β-catenin(5)

Cell-matrix interactions based on intracellular dynamics of the main cell-matrix adhesion components(6):

* cell surface receptor: integrin* matrix glycoprotein: fibronectin* actin cytoskeleton

Cell-matrix adhesion simulations using CompuCell3D

Adhesion force comparison between experimental data (left) and model (right)(6)

(6) Andasari and Chaplain (2012), MMNP, 7(1): 29–48

3D platform

2D platform

• Cell-matrix attachment and detachment model at cell front and rear, respectively, for migrating cells

• Incorporate stochastic aspects for the intracellular dynamics in the cell-cell and cell-matrix adhesion models

• Combine the cell-cell and cell-matrix adhesion models use Srcas an intermediate between E-cadherin (cell-cell adhesion) and integrin (cell-matrix adhesion)?

• Is polarization needed?

Stroma cells

Detached & migrated cells

Tumour

Stroma cells

Migrated cell

This model is for cell-matrix attachment at cell front