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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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Optimal condition of cell migration.A) Trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns), and B) bar graphs showing time-averaged cell migration speeds and error bars indicate standard deviations for nine different cases in A). Scale bar is 10 µm.
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pcbi-1002926-g006: Optimal condition of cell migration.A) Trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns), and B) bar graphs showing time-averaged cell migration speeds and error bars indicate standard deviations for nine different cases in A). Scale bar is 10 µm.

Mentions: Figure 6-A shows samples of trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns). First, simulated data were compared with different depolymerization times for the three values (rows) of polymerization times of 60, 180, and 300 s. Cell migration speed at each value (row) of polymerization time increases as the depolymerization time becomes larger (Figure 6-B). In the case of the polymerization time of 60 s, especially, the morphologies of cells were observed to be round. This phenomenon results from faster actin motor activity with the inclusion of a shorter polymerization process. Thereby, the occurrence of more frequent actin motor activity prevents the cell from stretching more than the other cases of polymerization times of 180 and 300 s. On the other hand, as the polymerization time becomes larger, the cell tends to stretch more and its morphology is changed to wider crescent-shape from the rounded shape. Next, simulated data were compared with different polymerization times for three values (columns) of depolymerization times of 1, 10, and 30 s (Figure 6-B). As for cases of depolymerization times of 1 and 10 s, cell migration speed increases as polymerization time decreases. In our model, a shorter polymerization process represents faster FA component (integrin and vinculin) renewal within FAs due to increased level of myosin II activation per FA. Contraction could pull these components out of FAs. It has been reported that faster turnover rates of vinculin and integrin due to further increase in actomyosin contractility are correlated with faster cell migration speed at the intermediated ligand surface density [45]. However, in case of depolymerization time of 30 s, cell migration speed takes a maximum at an intermediated value of polymerization time of 180 s, which suggest that a balance between adhesion strength and myosin II activity is required for optimal cell migration [45].


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)

Optimal condition of cell migration.A) Trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns), and B) bar graphs showing time-averaged cell migration speeds and error bars indicate standard deviations for nine different cases in A). Scale bar is 10 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002926-g006: Optimal condition of cell migration.A) Trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns), and B) bar graphs showing time-averaged cell migration speeds and error bars indicate standard deviations for nine different cases in A). Scale bar is 10 µm.
Mentions: Figure 6-A shows samples of trajectories and morphologies of simulated cell migrations along the planar surface of fibronectin surface density of 1140 molecules/µm2 for three hours under nine different cases of polymerization times with 60, 180, and 300 s (rows) and depolymerization times with 1, 10, and 30 s (columns). First, simulated data were compared with different depolymerization times for the three values (rows) of polymerization times of 60, 180, and 300 s. Cell migration speed at each value (row) of polymerization time increases as the depolymerization time becomes larger (Figure 6-B). In the case of the polymerization time of 60 s, especially, the morphologies of cells were observed to be round. This phenomenon results from faster actin motor activity with the inclusion of a shorter polymerization process. Thereby, the occurrence of more frequent actin motor activity prevents the cell from stretching more than the other cases of polymerization times of 180 and 300 s. On the other hand, as the polymerization time becomes larger, the cell tends to stretch more and its morphology is changed to wider crescent-shape from the rounded shape. Next, simulated data were compared with different polymerization times for three values (columns) of depolymerization times of 1, 10, and 30 s (Figure 6-B). As for cases of depolymerization times of 1 and 10 s, cell migration speed increases as polymerization time decreases. In our model, a shorter polymerization process represents faster FA component (integrin and vinculin) renewal within FAs due to increased level of myosin II activation per FA. Contraction could pull these components out of FAs. It has been reported that faster turnover rates of vinculin and integrin due to further increase in actomyosin contractility are correlated with faster cell migration speed at the intermediated ligand surface density [45]. However, in case of depolymerization time of 30 s, cell migration speed takes a maximum at an intermediated value of polymerization time of 180 s, which suggest that a balance between adhesion strength and myosin II activity is required for optimal cell migration [45].

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