Morphological and behavioral aspects of polarization

Cells migrating in a chemoattractant gradient exhibit a biased random walk, with migration persisting in the direction of the gradient because they turn less and less often than during random migration. If a cell is 

Both sets of observations indicate that the axis of orientation may be determined by an intracellular gradient throughout the entire cell, not just where the lamellipodium and/or the uropod are located. 

The progression to developing polarity in the distribution of DRMs begins with a uniform distribution of DRM components in resting cells. 

Activation with N-formyl peptides causes an initial rapid clustering of DRMs into discrete patches, followed by formation of a large cap over the cell body and uropod. This process requires myosin, since inhibitors of myosin prevent cap formation [351]. Localization of 3 -phosphoinositides in the lamellipodium may also be dependent upon the actin cytoskeleton [411], Thus polarization of the actin cytoskeleton appears to dictate the development of polarity of the membrane and signaling components. 

Most eukaryotic cells contain the major cytoskeletal protein, actin, which can exist as a monomer (G-actin) and reversibly polymerize into long filamentous structures (F-actin). The F-actin filament is polarized such that the rates of polymerization and depolymerization are different at the two ends. At the plus end (also called barbed end) monomer addition occurs readily, relative to the minus end (also called pointed end) where polymerization is less favored. In addition, the actin subunit binds adenine nucleotides and has an intrinsic ATPase activity. ATP-actin binds preferably at the plus end and, after incorporation into the filament, is converted to ADP-actin. These properties have a significant impact on the dynamics and stability of the filament [54, 293]. In the cell, polymerization and depolymerization are highly regulated reactions, this regulation being mediated by multiple actin-binding proteins. 

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