(49g) Effects of Convective Flow On Chemical Signaling in Cellular Systems

Interstitial flow in cell cultures plays an important role in many developmental and remodeling processes such as the lymphatic or blood capillary system formation. Interstitial flow also provides a nutrient transport in muscles or cartilages and promotes cell migration in lymphatic nodes during inflammatory responses. For example, interstitial flow can stimulate specific receptors (integrins) that then associate with Src (sarcoma) tyrosine kinase, which leads in a stable tyrosine kinase autophosporylation. Only under a combined influence of the convective flow and specific growth factors, endothelial cells form new capillaries. Other morphogens like epidermal growth factor probably independently regulate cell proliferation, which leads in capillary growth. The above mentioned examples demonstrate the importance of the convective flow in living tissues. These complex processes can be modeled within the framework of reaction-diffusion-convection equations that describe the transmission of chemical signals in cell populations. In this contribution, we will introduce mathematical models of the key reaction-transport processes around a spatially two-dimensional multicellular system (e.g. epithelium): the growth factor release and consumption, growth factor protease activation and deactivation, diffusion and convection transport of morphogens in the extracellular matrix, ligand-receptor binding and an intracellular reaction cascades leading to the growth factor synthesis. The intracellular cascade is represented by a simplified model of mitogen activated protein cascade that mediates signal transmission from the cell surface (receptors) to the intracellular domain (modification of transcription factors, protein phosphorylation etc.). Effects of the convective transport along the cellular layer on autocrine and paracrine cellular signaling will be presented. Interplay between the ligand (growth factor) transport and the ligand binding leads to a certain velocity of chemical signal transmission. Significant effects of the convective transport on this velocity will be presented. Due to the consideration of the convective transport, mathematical models can extend our insight into the chemical signaling in cellular systems based previously on reaction-diffusion equations. We believe that such mathematical models can be helpful for understanding developmental processes (vascular system formation) and also for understanding of cell motility in tissues (tissue injury, migration of cancer cells).