MULTISCALE TWO-DIMENSIONAL MODELING OF A MOTILE SIMPLE-SHAPED CELL.

Area of Science:

• Cell biology
• Biophysics
• Computational modeling

Background:

• Cell crawling is crucial for morphogenesis, cancer metastasis, and wound healing.
• Existing one-dimensional (1-D) models explain cell organization but lack the complexity for realistic movement.
• A need exists for more adequate two-dimensional (2-D) models to capture cell crawling dynamics.

Purpose of the Study:

• To develop and validate a multiscale 2-D computational model of cell crawling.
• To simulate the lamellipodium of a fish keratocyte, a model system for rapid cell movement.
• To couple key subprocesses of cell crawling, including protrusion, adhesion, and actin network dynamics.

Main Methods:

• Developed a multiscale 2-D computational model incorporating leading-edge protrusion/adhesion, a 2-D elastic actin network, rear-edge actin-myosin contraction, and actin transport.
• Utilized a finite element approach for numerical simulations.
• Coupled submodels addressing actin dynamics and transport within the lamellipodium.

Main Results:

• The 2-D model successfully reproduced observed cell shapes, forces, and crawling movements.
• Simulations explained experimental findings related to perturbations of the cell's actin machinery.
• The model provides a framework for understanding the interplay of forces and dynamics in cell motility.

Conclusions:

• The novel 2-D model offers a more realistic representation of cell crawling than previous 1-D models.
• The model's success in reproducing experimental data validates its approach.
• Future research can utilize this model to generate testable predictions and explore further questions in cell motility.