Limits...
Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Network.

Kim MC, Whisler J, Silberberg YR, Kamm RD, Asada HH - PLoS Comput. Biol. (2015)

Bottom Line: The dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood.This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers.This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues.

View Article: PubMed Central - PubMed

Affiliation: BioSystems and Micromechanics IRG, Singapore MIT Alliance for Research and Technology, Singapore; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

ABSTRACT
The dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood. Based on first principles, here we construct an individual-based, force-based computational model integrating four modules of 1) filopodia penetration dynamics; 2) intracellular mechanics of cellular and nuclear membranes, contractile actin stress fibers, and focal adhesion dynamics; 3) structural mechanics of ECM fiber networks; and 4) reaction-diffusion mass transfers of seven biochemical concentrations in related with chemotaxis, proteolysis, haptotaxis, and degradation in ECM to predict dynamic behaviors of filopodia that penetrate into a 3D ECM fiber network. The tip of each filopodium crawls along ECM fibers, tugs the surrounding fibers, and contracts or retracts depending on the strength of the binding and the ECM stiffness and pore size. This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers. This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues. Predicted average filopodia speed and that of the cell membrane advance agreed with experiments of 3D HUVEC migration at r(2) > 0.95 for diverse ECMs with different pore sizes and stiffness.

No MeSH data available.


Related in: MedlinePlus

Stochastic model of filopodia penetration dynamics in 3-D ECM fiber network.A) Schematic representation of three focal complexes (FCs) (‘a’) moving along ECM fibers in different directions. Free body diagram of the k-th filopodial node and the j-th node in the i-th fiber in the circle marked in A), where three and two external forces are acting, respectively. Note that, the sum of  and  is zero. B) a magnified view in A), showing the structure of FC including an integrin node at the filopodial membrane to an underlying ECM fiber, illustrating a stochastic ligand-receptor bonding process at the FC site. Note that, A) and B) represent top and side views, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4593642&req=5

pcbi.1004535.g002: Stochastic model of filopodia penetration dynamics in 3-D ECM fiber network.A) Schematic representation of three focal complexes (FCs) (‘a’) moving along ECM fibers in different directions. Free body diagram of the k-th filopodial node and the j-th node in the i-th fiber in the circle marked in A), where three and two external forces are acting, respectively. Note that, the sum of and is zero. B) a magnified view in A), showing the structure of FC including an integrin node at the filopodial membrane to an underlying ECM fiber, illustrating a stochastic ligand-receptor bonding process at the FC site. Note that, A) and B) represent top and side views, respectively.

Mentions: Finally, we have found through experiments that there exists another phase in filopodial dynamics: the tugging phase (S2 Video). The tip of a filopodium apparently crawls or slides along a nearby ECM fiber or multiple fibers (Fig 2A). We have observed that the binding site of FCs moves along the ECM fibers and that the bound ECM fibers are pushed or pulled by the filopodial tip. The adhesive force of FCs is sufficient to prevent the filopodium from retracting. This crawling or sliding can be viewed as a continuous process during which FCs form and rupture as they move along the ECM fibers, as depicted in Fig 2B.


Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Network.

Kim MC, Whisler J, Silberberg YR, Kamm RD, Asada HH - PLoS Comput. Biol. (2015)

Stochastic model of filopodia penetration dynamics in 3-D ECM fiber network.A) Schematic representation of three focal complexes (FCs) (‘a’) moving along ECM fibers in different directions. Free body diagram of the k-th filopodial node and the j-th node in the i-th fiber in the circle marked in A), where three and two external forces are acting, respectively. Note that, the sum of  and  is zero. B) a magnified view in A), showing the structure of FC including an integrin node at the filopodial membrane to an underlying ECM fiber, illustrating a stochastic ligand-receptor bonding process at the FC site. Note that, A) and B) represent top and side views, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593642&req=5

pcbi.1004535.g002: Stochastic model of filopodia penetration dynamics in 3-D ECM fiber network.A) Schematic representation of three focal complexes (FCs) (‘a’) moving along ECM fibers in different directions. Free body diagram of the k-th filopodial node and the j-th node in the i-th fiber in the circle marked in A), where three and two external forces are acting, respectively. Note that, the sum of and is zero. B) a magnified view in A), showing the structure of FC including an integrin node at the filopodial membrane to an underlying ECM fiber, illustrating a stochastic ligand-receptor bonding process at the FC site. Note that, A) and B) represent top and side views, respectively.
Mentions: Finally, we have found through experiments that there exists another phase in filopodial dynamics: the tugging phase (S2 Video). The tip of a filopodium apparently crawls or slides along a nearby ECM fiber or multiple fibers (Fig 2A). We have observed that the binding site of FCs moves along the ECM fibers and that the bound ECM fibers are pushed or pulled by the filopodial tip. The adhesive force of FCs is sufficient to prevent the filopodium from retracting. This crawling or sliding can be viewed as a continuous process during which FCs form and rupture as they move along the ECM fibers, as depicted in Fig 2B.

Bottom Line: The dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood.This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers.This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues.

View Article: PubMed Central - PubMed

Affiliation: BioSystems and Micromechanics IRG, Singapore MIT Alliance for Research and Technology, Singapore; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

ABSTRACT
The dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood. Based on first principles, here we construct an individual-based, force-based computational model integrating four modules of 1) filopodia penetration dynamics; 2) intracellular mechanics of cellular and nuclear membranes, contractile actin stress fibers, and focal adhesion dynamics; 3) structural mechanics of ECM fiber networks; and 4) reaction-diffusion mass transfers of seven biochemical concentrations in related with chemotaxis, proteolysis, haptotaxis, and degradation in ECM to predict dynamic behaviors of filopodia that penetrate into a 3D ECM fiber network. The tip of each filopodium crawls along ECM fibers, tugs the surrounding fibers, and contracts or retracts depending on the strength of the binding and the ECM stiffness and pore size. This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers. This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues. Predicted average filopodia speed and that of the cell membrane advance agreed with experiments of 3D HUVEC migration at r(2) > 0.95 for diverse ECMs with different pore sizes and stiffness.

No MeSH data available.


Related in: MedlinePlus