How did cells get their size?

Cells exercise size homeostasis, and the origins of their ability to do so is the topic of this essay. Before there were cells, there were protocells. The most basic questions about protocells as objects are: What were they made of, and how big were they? Asking how big they were implies that the answer to the first part includes a boundary. The best candidate for that boundary is a self-assembling lipid bilayer. Therefore, protocells are defined here as Darwinian liposomes-bilayer vesicles with mutable on-board replicases linked to phenotypes. Because liposomes undergo spontaneous fission and fusion, and are subject to osmotic forces, size regulation in the earliest protocells would essentially have been liposome physics. For successful protocells, averting osmotic lysis would have been the first order of business. However, from the outset size mattered too, because of sex and reproduction (i.e., genome mixing and genome copying in entities with phenotypes). Protocell fission and fusion would have blended seamlessly into protocell sex and reproduction, making any gene product that furnished control over protocell size changes doubly adaptive. A recurrent theme is the feedback role of bilayer tension in protocell size control. Ways in which primitive peptides and their aggregates (e.g., channels) might have allowed liposomes to gain improved volume and surface area homeostasis are suggested. Domain-swapped proteins that polymerize as filaments are discussed as the origin of cytoskeleton structures that diversify and stabilize liposome shapes and sizes. Throughout, attention is paid to the question of set points for cell size. Copyright 2002 Wiley-Liss, Inc.