(512c) Elucidating Design Principles Underlying Attractive and Repulsive Gradient Sensing in Eukaryotic Chemotaxis

Many cells  respond to gradients of concentrations of  chemicals in their environment  by exhibiting directional migration, a process known as chemotaxis. This  widely occuring process plays very important biological and physiological roles. In many cases, the movement is up-gradient, and the process is referred to as chemoattraction, and in some other cases, the movement is down-gradient and the process is referred to as chemorepulsion. It has been experimentally found that different eukaryotic cells are capable of both chemoattraction and chemorepulsion, either to different chemicals, or in some cases to the same chemical but under different conditions. It is thus important to examine what features in the wiring of the signalling networks and their organization allow the cell to exhibit both these features, and how this affects the signal transduction in each case. 

     We do this by systematically analyzing two cases, motivated by their postulation and discussion in the experimental literature. The first is that of a “polarity switch” and the second is the role of competing signalling effects at the gradient sensing. For each of these cases, we will discuss how these basic network wiring possibilities may allow for the cell to exhibit attractive and repulsive response, and then examine how this works upstream of different qualitative signalling behaviour such as adaptation and spontaneous polarization. This is achieved by “connecting” the relevant modules in-silico.  This systematic approach reveals the behaviour of each design feature, the capabilities and constraints involved. This approach provides a "systems skeleton" for understanding how cell signalling is organized to exhibit multiple migratory responses, and how cell may either conform to or bypass these constraints

 We will then discuss the implication of our various results in the context of the known signalling networks of different concrete eukaryotic cell types. Overall this provides a design framework for examining and elucidating design principles of attractive/repulsive gradient sensing in multiple systems and a basis for controlling cell migration based on this feature.