3D numerical modeling of cell migration and cell-cell interaction

Mousavi, Seyed Jamaleddin
Hamdy Doweidar, Mohamed (dir.)

Universidad de Zaragoza, EINA, 2012
Departamento de Ingeniería Mecánica, Área de Mec. de Medios Contínuos y Teor. de Estructuras

Máster Universitario en Ingeniería Biomédica

Resumen: Cell migration has an important role in physiological, biological and pathological processes such as tissue morphogenesis, cell differentiation, cell proliferation, cancer development, wound healing, as well as in tissue engineering applications [1,2]. Although cell behavior during migration is not completely clear for scientists yet, it has conclusively been known that mechanical and biochemical factors strongly affect cell locomotion. Mechanical changes in a substrate, such as topographical features, boundary conditions and stiffness distribution of substrate are all thought to guide and control cell migration. There are many 2D models describing cell behavior on a substrate [3], but there are only few 3D models for this purpose [4]. Majority of them just describe a single cell migration [4], while others study the behavior of high cell populations [5]. One major problem with some of these models is that they fail to properly balance the active locomotive forces acting on the cell or generated by the cell, in some cases the models do not even include them. Some models have an active force that moves the cell, but there is no discussion on where that force is applied. The model described by Borau et al. considers the maximum principal stess for the reorientation of cell and cytoskeleton which is not accurate enough [4]. In this work we will present an improved 3D computational model to investigate the effects of the mechanical properties of the substrate on cell migration. The main objective of this project is to understand the effect of substrate stiffness on cell migration, traction force, velocity and etc. Besides, we will study how deeply the cell feels during surface migration and how the cells interact each other when they are embedded in the same substrate. To validate our model, apart from comparing the obtained results with previous experimental [6] and numerical models [4,5], we will implement experimental part which includes preparation of 3D gel with desired boundary conditions and monitoring of cell behavior during migration. To monitor the cell behavior we are going to use fluorescence microscopy to record the cell movement. This experimental part will be performed by collaboration with laboratory of Aragon Institute of Engineering Research (i3A). Refrences [1] H. Behesti and S. Marino. Cerebellar granule cells: Insights into proliferation, differentiation, and role in medulloblastoma pathogenesis. Journal Applied Physiology, 41:435445, 2009. [2] P. Martin. Wound healing: aiming for perfect skin regeneration. Science, 276:75 81, 1997. [3] P. Moreo, J.M. Garcia-Aznar, and M. Doblaré. Modeling mechanosensing and its e˙ect on the migration and proliferation of adherent cells. Acta Biomaterialia, 4:613621, 2008. [4] C. Borau, R.D. Kamm, and J.M. García-Aznar. Mechano-sensing and cell migration: a 3d model approach. Journal Physical Biology, 8:107888, 2011. [5] E. Palsson. A three-dimensional model of cell movement in multicellular systems. Future Generation Computer System, 17:835852, 2001. [6] E. Hadjipanayi, V. Mudera, and R.A. Brown. Guiding cell migration in 3d: A collagen matrix with graded directional sti˙ness. Cell Motility and the Cytoskeleton, 66:435445, 2009.

Palabra(s) clave (del autor): 3d finite element simulation ; cell migration ; cell mechano-sensing ; substrate stiffness ; cell-substrate interaction ; cell-cell interaction

Tipo de Trabajo Académico: Trabajo Fin de Master