Abstract
Cell Migration associated with cell shape changes are of central importance in many biological processes ranging from morphogenesis to metastatic cancer cells. Cell movement is a result of cyclic changes of cell morphology due to effective forces on cell body, leading to periodic fluctuations of the cell length and cell membrane area. It is well-known that the cell can be guided by different effective stimuli such as mechanotaxis, thermotaxis, chemotaxis and/or electrotaxis. Regulation of intracellular mechanics and cell’s physical interaction with its substrate rely on control of cell shape during cell migration. In this notion, it is essential to understand how each natural or external stimulus may affect the cell behavior. Therefore, a three-dimensional (3D) computational model is here developed to analyze a free mode of cell shape changes during migration in a multi-signaling micro-environment. This model is based on previous models that are presented by the same authors to study cell migration with a constant spherical cell shape in a multi-signaling substrates and mechanotaxis effect on cell morphology. Using the finite element discrete methodology, the cell is represented by a group of finite elements. The cell motion is modeled by equilibrium of effective forces on cell body such as traction, protrusion, electrostatic and drag forces, where the cell traction force is a function of the cell internal deformations. To study cell behavior in the presence of different stimuli, the model has been employed in different numerical cases. Our findings, which are qualitatively consistent with well-known related experimental observations, indicate that adding a new stimulus to the cell substrate pushes the cell to migrate more directionally in more elongated form towards the more effective stimuli. For instance, the presence of thermotaxis, chemotaxis and electrotaxis can further move the cell centroid towards the corresponding stimulus, respectively, diminishing the mechanotaxis effect. Besides, the stronger stimulus imposes a greater cell elongation and more cell membrane area. The present model not only provides new insights into cell morphology in a multi-signaling micro-environment but also enables us to investigate in more precise way the cell migration in the presence of different stimuli.
Highlights
Cell shape change during cell migration is a key factor in many biological processes such as embryonic development [1,2,3], wound healing [4,5,6] and cancer spread [7,8,9]
This causes a decrease in the cell elongation and Cell Morphological Index (CMI) once the cell centroid is around imaginary equilibrium plane (IEP)
Because the cell extends pseudopods in the vertical direction of chemical gradient, the cell elongation and CMI slightly increases, which is more obvious for greater chemical effective factor (Fig 12)
Summary
Cell shape change during cell migration is a key factor in many biological processes such as embryonic development [1,2,3], wound healing [4,5,6] and cancer spread [7,8,9]. Many attempts have been made to explain cell shape changes associated with directed cell migration, but the mechanism behind it is still not well understood. It is well-known that cell migration is fulfilled via successive changes of the cell shape. Several factors are believed to control cell shape changes and cell migration including intrinsic cue such as mechanotaxis or extrinsic stimuli such as chemotaxis, thermotaxis and electrotaxis
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