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.
Highlights
Understanding cell migration mechanisms is a critical issue in many biophysical phenomena, including angiogenesis, tumor growth, metastasis, and wound healing [1,2,3]
Afterwards, contractile bundles of actin filaments, called stress fibers (SFs), extend from nascent focal adhesion (FA) and some of which connect to the nucleus [11]
Afterwards, actin stress fibers extend from nascent focal adhesions, some of which connect to the nucleus
Summary
Understanding cell migration mechanisms is a critical issue in many biophysical phenomena, including angiogenesis, tumor growth, metastasis, and wound healing [1,2,3]. Cell migration is a complex multifaceted process, triggered by chemotaxis and haptotatic responses from the extracellular environment [4]. Focal adhesions (FAs) are assembled between the lamellipodium base and the extracellular matrix (ECM). FAs are composed of FA molecules (such as FAK, paxillin, vinculin, Zyxin, VASP, and talin), and transmembrane proteins, especially integrins avb and avb that link the ECM to the cytoskeleton via FA molecules [9,10]. Afterwards, contractile bundles of actin filaments, called stress fibers (SFs), extend from nascent FAs and some of which connect to the nucleus [11]. The corresponding motor activity exerts force on the FA’s fore and aft [12], enabling the generation of a traction force and the release of FAs in the rear of the cell, creating the cell body’s forward movement
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