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Dynamic modeling of cell migration and spreading behaviors on fibronectin coated planar substrates and micropatterned geometries.

Kim MC, Neal DM, Kamm RD, Asada HH - PLoS Comput. Biol. (2013)

Bottom Line: The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading.In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges.This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays.

View Article: PubMed Central - PubMed

Affiliation: BioSystem & Micromechanics IRG, Singapore MIT Alliance Research Technology, Singapore. mincheol@mit.edu

ABSTRACT
An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (∼1140 molecules/µm(2)) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays.

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Contour plots of traction (or FA) force on ventral cell surfaces.Spreading cells on three fibronectin coated micropatterns of A) disk, B) pacman and C) crossbow shapes. Plots also reveal distributions of oriented ventral SFs and SFs connected to the nucleus (red lines). N indicates a nucleus and scale bar is 10 µm. D) Temporal variations of total traction stress per a cell on three different micropatterns, and E) time-averaged total traction stress of the cell for one hour is high in the order of the crossbow, pacman and disk shapes.
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pcbi-1002926-g004: Contour plots of traction (or FA) force on ventral cell surfaces.Spreading cells on three fibronectin coated micropatterns of A) disk, B) pacman and C) crossbow shapes. Plots also reveal distributions of oriented ventral SFs and SFs connected to the nucleus (red lines). N indicates a nucleus and scale bar is 10 µm. D) Temporal variations of total traction stress per a cell on three different micropatterns, and E) time-averaged total traction stress of the cell for one hour is high in the order of the crossbow, pacman and disk shapes.

Mentions: The second set of cell spreading simulation was intended to compare the integrated model against the recent experimental data published by Tseng et al.[18]. They developed a method to micropattern ECM proteins on poly-acrylamide gels in order to impinge on cell morphology and mechanics simultaneously, and have reported that measured traction forces differ considerably depending on the shape of micropatterns. In particular, in the case of the crossbow shaped micropatterns, concentrated cell traction forces are repeatedly located in the bottom part of the vertical bar. The simulation of the integrated model also showed similar spreading cell morphologies on micropatterned models and traction force distributions on the cell surface (Figure 4-A, B and C).


Dynamic modeling of cell migration and spreading behaviors on fibronectin coated planar substrates and micropatterned geometries.

Kim MC, Neal DM, Kamm RD, Asada HH - PLoS Comput. Biol. (2013)

Contour plots of traction (or FA) force on ventral cell surfaces.Spreading cells on three fibronectin coated micropatterns of A) disk, B) pacman and C) crossbow shapes. Plots also reveal distributions of oriented ventral SFs and SFs connected to the nucleus (red lines). N indicates a nucleus and scale bar is 10 µm. D) Temporal variations of total traction stress per a cell on three different micropatterns, and E) time-averaged total traction stress of the cell for one hour is high in the order of the crossbow, pacman and disk shapes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585413&req=5

pcbi-1002926-g004: Contour plots of traction (or FA) force on ventral cell surfaces.Spreading cells on three fibronectin coated micropatterns of A) disk, B) pacman and C) crossbow shapes. Plots also reveal distributions of oriented ventral SFs and SFs connected to the nucleus (red lines). N indicates a nucleus and scale bar is 10 µm. D) Temporal variations of total traction stress per a cell on three different micropatterns, and E) time-averaged total traction stress of the cell for one hour is high in the order of the crossbow, pacman and disk shapes.
Mentions: The second set of cell spreading simulation was intended to compare the integrated model against the recent experimental data published by Tseng et al.[18]. They developed a method to micropattern ECM proteins on poly-acrylamide gels in order to impinge on cell morphology and mechanics simultaneously, and have reported that measured traction forces differ considerably depending on the shape of micropatterns. In particular, in the case of the crossbow shaped micropatterns, concentrated cell traction forces are repeatedly located in the bottom part of the vertical bar. The simulation of the integrated model also showed similar spreading cell morphologies on micropatterned models and traction force distributions on the cell surface (Figure 4-A, B and C).

Bottom Line: The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading.In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges.This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays.

View Article: PubMed Central - PubMed

Affiliation: BioSystem & Micromechanics IRG, Singapore MIT Alliance Research Technology, Singapore. mincheol@mit.edu

ABSTRACT
An integrative cell migration model incorporating focal adhesion (FA) dynamics, cytoskeleton and nucleus remodeling, actin motor activity, and lamellipodia protrusion is developed for predicting cell spreading and migration behaviors. This work is motivated by two experimental works: (1) cell migration on 2-D substrates under various fibronectin concentrations and (2) cell spreading on 2-D micropatterned geometries. These works suggest (1) cell migration speed takes a maximum at a particular ligand density (∼1140 molecules/µm(2)) and (2) that strong traction forces at the corners of the patterns may exist due to combined effects exerted by actin stress fibers (SFs). The integrative model of this paper successfully reproduced these experimental results and indicates the mechanism of cell migration and spreading. In this paper, the mechanical structure of the cell is modeled as having two elastic membranes: an outer cell membrane and an inner nuclear membrane. The two elastic membranes are connected by SFs, which are extended from focal adhesions on the cortical surface to the nuclear membrane. In addition, the model also includes ventral SFs bridging two focal adhesions on the cell surface. The cell deforms and gains traction as transmembrane integrins distributed over the outer cell membrane bond to ligands on the ECM surface, activate SFs, and form focal adhesions. The relationship between the cell migration speed and fibronectin concentration agrees with existing experimental data for Chinese hamster ovary (CHO) cell migrations on fibronectin coated surfaces. In addition, the integrated model is validated by showing persistent high stress concentrations at sharp geometrically patterned edges. This model will be used as a predictive model to assist in design and data processing of upcoming microfluidic cell migration assays.

Show MeSH
Related in: MedlinePlus