Chemoattractant gradients

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. 

Narang A, Subramanian KK, Lauffenburger DA. A mathematical model for chemoattractant gradient sensing based on receptor-regulated membrane phospholipid signaling dynamics. Ann. Bio-med. Eng. 2001 29 677-691. 

For CKs to act in vivo, they require a solid phase in which normal conditions of blood flow would be unable to wash away the chemoattractant gradient. In this manner, CKs secreted by each cell trafficking through a vessel are sequestered and maintained by stable components of the extracellular matrix, such as proteoglycans. This model of CK action in leukocyte migration is summarized in Figure 22-33. 

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... 

Xu, X., Meier-Schellersheim, M., Jiao, X., Nelson, L. E., and Jin, T. (2005) Quantitative imaging of single live cells reveals spatiotem-poral dynamics of multistep signaling events of chemoattractant gradient sensing in Dictyostelium. Mol. Biol. Cell 16, 676-688. 

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). 

---