The size and metabolic rate of cells affect processes from the molecular to the organismal level. We present a quantitative, theoretical framework for studying relationships among cell volume, cellular metabolic rate, body size, and whole-organism metabolic rate that helps reveal the feedback between these levels of organization. We use this framework to show that average cell volume and average cellular metabolic rate cannot both remain constant with changes in body size because of the well known body-size dependence of whole-organism metabolic rate. Based on empirical data compiled for 18 cell types in mammals, we find that many cell types, including erythrocytes, hepatocytes, fibroblasts, and epithelial cells, follow a strategy in which cellular metabolic rate is body size dependent and cell volume is body size invariant. We suggest that this scaling holds for all quickly dividing cells, and conversely, that slowly dividing cells are expected to follow a strategy in which cell volume is body size dependent and cellular metabolic rate is roughly invariant with body size. Data for slowly dividing neurons and adipocytes show that cell volume does indeed scale with body size. From these results, we argue that the particular strategy followed depends on the structural and functional properties of the cell type. We also discuss consequences of these two strategies for cell number and capillary densities. Our results and conceptual framework emphasize fundamental constraints that link the structure and function of cells to that of whole organisms.allometry ͉ body mass ͉ cell number ͉ cell size ͉ cell types M any biological studies focus on how cellular properties affect the structure and function of the whole organism. Little attention, however, has been paid to the inverse problem: to what extent do whole-organism anatomy and physiology influence cell size and function? Both research directions are necessary to develop a comprehensive, integrated understanding of biological systems.Of particular relevance is the scaling of cell size and cellular metabolic rate with body size. Both have important consequences for cellular and whole-body properties (1, 2), such as numbers of organelles, cells, and capillaries (1-5). There is little empirical consensus or theoretical understanding of how the numbers, sizes, and metabolic rates of cells change with body size. This lack of consensus is true despite numerous studies of cellular processes, including extensive work on cell size and genome length (1, 2, 5-20), across a broad spectrum of different-sized mammals and other organisms. Schmidt-Nielsen (21) concluded that ''. . . large and small animals have cells that are roughly of the same size. . . '' so that ''. . . a large organism is not made up of larger cells, but of a larger number of cells of roughly the same size.'' This is the view predominantly expressed, or tacitly assumed, in much of the literature. However, exceptions to this pattern for certain cell types have been reported for almost a century. For example, emp...
