Cell memory and adaptation in chemotaxis.

Abstract

How cells direct motion in response to environmental stimuli has long fascinated biologists. Chemotaxis, the migration guided by chemical gradients, is a fundamental property of many cells and plays important roles in physiology and pathological conditions. One of the best-studied models for chemotaxis is the social amoeba Dictyostelium discoideum. In nutrient-deprived environments, Dictyostelium cells initiate a developmental program that allows them to aggregate and form fruiting bodies. During this process, cells periodically secrete cAMP, which functions as a chemoattractant to guide their migration. In a field of cells, periodic waves of cAMP are initiated from an aggregation center every ∼6 min and sweep out in concentric circles or spirals. As the waves approach cells, they first experience a spatial gradient, with the high side facing the center. Thereafter, because the spatial profile of the waves is symmetric (1), as the peak of the wave passes cells are faced with an equivalent but oppositely directed gradient (Fig. 1). Despite this change of direction, the overall movement of cells is toward the center. How chemotactic cells are able to sense the approaching wave but appear to ignore it as it moves away is known as the “back of the wave” problem, and has perplexed the field for some time. Two possible explanations have been proposed. The first explanation relies on the fact that cells adapt—or cease to respond—to constant levels of stimuli (2). Therefore, cells are more sensitive during the rising phase of the wave, when the concentration of the chemoattractant is increasing over time, and lose sensitivity at the back of the wave when the concentration is declining. The second explanation notes that over time cells develop an intrinsic polarity with well-defined anterior and posterior regions, and this polarity allows cells to maintain their direction when the guidance cue fluctuates (3). The relative importance of each process in allowing cells to move unidirectionally in periodic waves has not been known, although both suggest that in addition to the spatial profile, cells make use of the temporal information of the concentration. In PNAS, Skoge et al. address this question through careful analysis of migration and the corresponding signaling activities of cells responding to spatiotemporal patterns of cAMP generated by a novel microfluidic device (4). The authors show that cells display a memory that persists beyond—but is modulated by—the adaptation process. This interplay between memory and adaptation allows cells to move against the gradient in the back of the wave.