Mohamed Hamdy Doweidar, Seyed Jamaleddin Mousavi
Group of Structural Mechanics and Materials Modelling (GEMM), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.
Mechanical Engineering Department, School of Engineering and Architecture (EINA), University of Zaragoza, Spain.
Cell morphology is a key aspect in many biological processes such as morphogenesis, tumor growth and wound healing. Among other cues, mechanical characteristic of the surrounding micro-environment can control the cell morphology. It is well known that traction forces transmitted to the extracellular matrix (ECM) through cell focal adhesions and integrins play a fundamental role in this process by rearranging the cell cytoskeleton (CSK). In this work we have developed a novel 3D computational model to comprehensively predict the evolution of cell morphology during migration due to mechanotaxis.
A discrete methodology is here chosen by which the cell is represented by a group of finite elements. Therefore, during migration, the cell shape can be efficiently remodeled in a free mode. The present model is developed based on equilibrium of the effective forces over the cell body; the traction force, the protrusion force and the drag force. The cell traction force is governed by the cell internal deformation. The random protrusion force is generated by actin polymerization. The drag force is the substrate viscous resistance.
Correlated with experimental observations, the present model illustrates that the morphology of an adherent cell can be controlled by substrate stiffness and boundary conditions. Our findings indicate that within an unconstrained substrate with a soft (several kPa) and hard (>200 kPa) stiffnesses, the cell is unable to adhere or penetrate into the substrate so that the cell remains mainly rounded without any specific preference of migration direction. In contrast, when a cell is located within a substrate with an intermediate (10 kPa) and rigid (100 kPa) stiffnesses the cell can actively adhere to the substrate migrating towards the constrained surfaces. It can be concluded that in the intermediate and rigid substrates the higher the traction force, the greater the cell elongation, the larger the cell membrane area, and the less random the cell alignment.
Keywords: Finite Element Method, Cell Morphology, Cell migration, Mechanotaxis.
Acknowledgements: The authors gratefully acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (MINECO MAT2013-46467-C4-3-R) and the CIBER-BBN initiative. CIBER-BBN is financed by the Instituto de SaludCarlos III with assistance from the European Regional Development Fund.