Role of target geometry in phagocytosis

Abstract

Phagocytosis is a principal component of the body's innate immunity in which macrophages internalize targets in an actin-dependent manner. Targets vary widely in shape and size and include particles such as pathogens and senescent cells. Despite considerable progress in understanding this complicated process, the role of target geometry in phagocytosis has remained elusive. Previous studies on phagocytosis have been performed using spherical targets, thereby overlooking the role of particle shape. Using polystyrene particles of various sizes and shapes, we studied phagocytosis by alveolar macrophages. We report a surprising finding that particle shape, not size, plays a dominant role in phagocytosis. All shapes were capable of initiating phagocytosis in at least one orientation. However, the local particle shape, measured by tangent angles, at the point of initial contact dictates whether macrophages initiate phagocytosis or simply spread on particles. The local shape determines the complexity of the actin structure that must be created to initiate phagocytosis and allow the membrane to move over the particle. Failure to create the required actin structure results in simple spreading and not internalization. Particle size primarily impacts the completion of phagocytosis in cases where particle volume exceeds the cell volume.drug delivery ͉ macrophages ͉ membrane ͉ shape P hagocytosis is a principal component of the body's innate immunity in which macrophages and other antigenpresenting cells internalize large (Ͼ0.5 m) particulate targets (1). Examples of targets include pathogens such as rod-shaped Escherichia coli and Bacillus anthracis and spiral-shaped Campylobacter jejuni, disk-shaped senescent cells such as aged erythrocytes, and airborne particles such as dust and pollen, all of which vary widely in both shape and size. Because macrophages in the human body encounter targets with such diversity, the question has long been asked, how does target geometry impact phagocytosis? Several studies have been conducted specifically to address this question; however, a generalized answer is still lacking. The main reason behind this shortcoming is that all phagocytosis studies have been performed with spherical targets (2-7). Exclusive use of spherical particles originated partly because of a presumption that size is the principal parameter of interest and partly because of difficulties in fabricating nonspherical particles of controlled dimensions. Use of spherical particles not only concealed the role of particle shape in phagocytosis but also created an inaccurate picture of the actual role of particle size because all parameters that describe size (volume, surface area, etc.) scale with particle radius, leaving one wondering as to which parameter is of fundamental consequence in phagocytosis. Accordingly, the precise roles of target size and shape in phagocytosis, despite their high relevance, remain largely unknown.Herein, we report, using alveolar macrophages as model phagocytes and polystyrene (PS) particles o...

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“…These examples present very peculiar non-spherical structures. [ 99 ] In the case of more elongated particles, the region where the macrophages fi rstly adhere dictates if the cells will be capable to internalize the particles or just spread onto their surface. Champion and Mitragotri [ 99 ] studied the effect of size and shape (spheres, oblate ellipsoids, prolate ellipsoids, elliptical disks, rectangular disks and UFO-like shape particles) in phagocytosis, using polystyrene particles.…”

“…[ 99 ] In the case of more elongated particles, the region where the macrophages fi rstly adhere dictates if the cells will be capable to internalize the particles or just spread onto their surface. Champion and Mitragotri [ 99 ] studied the effect of size and shape (spheres, oblate ellipsoids, prolate ellipsoids, elliptical disks, rectangular disks and UFO-like shape particles) in phagocytosis, using polystyrene particles. For elliptical discs, if the initial contact between particles and cells occurs at the pointed end, the particles are internalized in a few minutes, but if the contact is done on the fl at lateral region, the macrophage is not able to internalize the particle ( Figure 7 I).…”