Chemoattractant gradients Chemotaxiss

Figure 4.10. Changes in cell shape during phagocytosis and chemotaxis. Both of these neutrophil functions require protrusion of pseudopodia (either to engulf the bacterium or else to move the cell along a chemoattractant gradient) followed by contraction.

Firtel, R. A., and Chung, C. Y. (2000). The molecular genetics of chemotaxis Sensing and responding to chemoattractant gradients. Bioessays 22, 603-615. 

An important characteristic of cancer cells is their ability to detect chemoattractant gradients and move in response to them (1, 2). It has been shown that chemotaxis plays a critical role in metastasis, where cancer cells detect chemoattractant gradients fonnd within the tnmor microenvironment (3, 4) and distant tissnes... 

Computer-based quantitative models that address the complexity of a signaling network with its many interacting components are valuable for studies of chemotaxis. Chapter 30 summarizes a computer program that quantifies movement of amoeboid cells. Chapter 31 introduces mathematical calculations on experimentally generated chemoattractant gradients. Finally, Chapters 32 and 33 introduce two computational models that are constructed to simulate spatial-temporal dynamics of signaling networks for eukaryotic chemosensing. 

The common denominator of all these mechanisms is that their end result is a directional change up a chemoattractant gradient or down a chemorepellent gradient. These mechanisms should be distinguished from chemokinesis (also termed orthokinesis [7]), which is a mechanism of response that does not involve directional changes and is, therefore, not a part of the broad definition of chemotaxis. In chemokinesis, the linear velocity of the cell or organism is altered by the stimulus [7]. Chemotaxis and chemokinesis may occur in parallel, as in the case of the response of sperm cells to substances secreted from the egg (Chapter 7). 

The other assay therefore employs a one-dimensional chemoattractant gradient, established in a Zigmond chamber, which was originally designed for the evaluation of leukocyte chemotaxis [194]. In this chamber, which is built from two parallel, rectangular wells separated by a wall (Figure 10), a one-dimensional concentration gradient is... 

Neutrophils may move at speeds of up to 20 /tm min-1 in response to chemoattractants such as denatured proteins, lipids, peptides or C5a. Movement may be defined either as chemokinesis, which is generalised (non-directional) locomotive activity, or as chemotaxis, which is orientation and directional migration up a concentration gradient. A concentration difference at opposite ends of the cell of only 1% is sufficient to activate such directional movement. However, neutrophils do not respond chemotactical-ly to static gradients of chemoattractants, and both temporal and directional changes in chemoattractant concentrations are required. 

To determine the optimal concentration for collecting the invasive population, it is often necessary to perform dose response experiments and try a range of chemoattractant amounts. We have found that for EGF, the optimal concentration in the in vivo invasion assay is 25 nM while for the in vitro Boyden chamber chemotaxis it is 5 nM. The difference can be explained by different diffusion properties of the gradient emanating from a tip of a needle into live tissue vs. EGF in a buffer being directly accessible to migrating cells across pores in a filter. By the same token, the optimal... 

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