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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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Cell migration along the planar surface of fibronectin.A) Simulated trajectories of cell migrations on fibronectin coated substrates under five different ligand surface densities of 19.4, 192, 568, 1140 and 1522 molecules/µm2. The black lines indicate trajectories of nuclei for the first three hours, B) comparison of average cell migration speeds: the simulation model vs. experiment data by Palecek et al.[17]. Average speed and standard error of mean (N = 5) are shown for the five different ligand surface densities, and C). linear regression (R2 = 0.767) of simulated migration speed vs. experimental migration speed.
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pcbi-1002926-g003: Cell migration along the planar surface of fibronectin.A) Simulated trajectories of cell migrations on fibronectin coated substrates under five different ligand surface densities of 19.4, 192, 568, 1140 and 1522 molecules/µm2. The black lines indicate trajectories of nuclei for the first three hours, B) comparison of average cell migration speeds: the simulation model vs. experiment data by Palecek et al.[17]. Average speed and standard error of mean (N = 5) are shown for the five different ligand surface densities, and C). linear regression (R2 = 0.767) of simulated migration speed vs. experimental migration speed.

Mentions: Figure 3-A show samples of trajectories and morphologies of simulated cell migrations along the planar surface of five different fibronectin surface densities of 19.4, 192, 568, 1140 and 1522 molecules µm−2 for three hours (see Videos S1, S2, S3, S4 and S5). The ligand densities used for the simulations matched those of the available experiment data; ligand surface densities of fibronectin were converted from fibronectin plate concentrations (µg ml−2) using the relationship between plating concentration and ligand surface density of fibronectin [41]. First the total path length of each trajectory was obtained and was divided by the travelling time, 3 hours, to obtain the time-averaged cell migration speed. In the experiments, the speed of CHO cell migration was monitored in every 15 minutes, and was time averaged over the entire migration period (12 h) for each of fibronectin concentrations. Figure 3-B compares the average migration speed between the experiment and simulations. Here an error bar indicates a SE (standard error) of means.


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)

Cell migration along the planar surface of fibronectin.A) Simulated trajectories of cell migrations on fibronectin coated substrates under five different ligand surface densities of 19.4, 192, 568, 1140 and 1522 molecules/µm2. The black lines indicate trajectories of nuclei for the first three hours, B) comparison of average cell migration speeds: the simulation model vs. experiment data by Palecek et al.[17]. Average speed and standard error of mean (N = 5) are shown for the five different ligand surface densities, and C). linear regression (R2 = 0.767) of simulated migration speed vs. experimental migration speed.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002926-g003: Cell migration along the planar surface of fibronectin.A) Simulated trajectories of cell migrations on fibronectin coated substrates under five different ligand surface densities of 19.4, 192, 568, 1140 and 1522 molecules/µm2. The black lines indicate trajectories of nuclei for the first three hours, B) comparison of average cell migration speeds: the simulation model vs. experiment data by Palecek et al.[17]. Average speed and standard error of mean (N = 5) are shown for the five different ligand surface densities, and C). linear regression (R2 = 0.767) of simulated migration speed vs. experimental migration speed.
Mentions: Figure 3-A show samples of trajectories and morphologies of simulated cell migrations along the planar surface of five different fibronectin surface densities of 19.4, 192, 568, 1140 and 1522 molecules µm−2 for three hours (see Videos S1, S2, S3, S4 and S5). The ligand densities used for the simulations matched those of the available experiment data; ligand surface densities of fibronectin were converted from fibronectin plate concentrations (µg ml−2) using the relationship between plating concentration and ligand surface density of fibronectin [41]. First the total path length of each trajectory was obtained and was divided by the travelling time, 3 hours, to obtain the time-averaged cell migration speed. In the experiments, the speed of CHO cell migration was monitored in every 15 minutes, and was time averaged over the entire migration period (12 h) for each of fibronectin concentrations. Figure 3-B compares the average migration speed between the experiment and simulations. Here an error bar indicates a SE (standard error) of means.

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