Dynamic Modeling of Cell Migration and Spreading Behaviors on Fibronectin Coated Planar Substrates and Micropatterned Geometries

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/µm2) 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.

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

“…4 a). This hourglass shape has been observed in various cell migration experiments (8,13,25,39). Interestingly, our model predicts that E 1 and E 2 are mostly tensile and compressive, respectively, consistent with the experimental patterns of strain maps derived based on the triangulation between the individual, naturally present dense chromatin foci (Fig.…”

Strain Reduction of Human Gingival Fibroblasts Induces the ATP Pathway

“…Three weeks later, a significant bone loss on the periodontal aspect of alveolar bone that extends toward bone crest was recorded [4,18]. In the present study, human gingival fibroblasts (HGF) that were seeded on collagen coated culture dishes normally developed traction forces between the HGF cells and collagen [27][28][29]. Detachment of the collagen coat from culture dish surface produced an immediate sharp rise of extracellular ATP, an increased influx of calcium and a significant change in cell shape.…”

Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results

“…Only recently attempts to model cell migration in a mechanistic way have been introduced. Kim et al [205] integrated focal adhesion dynamics, cell membrane and nuclear remodeling, actin motor activity, and lamellipodia protrusion reflecting the 3D spatiotemporal dynamics of both cell spreading and migration. A comprehensive and detailed 2D model for cell migration in ECM was developed by Tozluoglu et al [206], who analyzed the cell migration speed governed by the interplay between ECM structure, adhesion strength and CSK contractility.…”