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Building the cell: design principles of cellular architecture
Susanne M. Rafelski and Wallace F. Marshall

Abstract | The astounding structural complexity of a cell arises from the action of a relatively small number of genes, raising the question of how this complexity is achieved. Self-organizing processes combined with simple physical constraints seem to have key roles incontrolling organelle size, number, shape and position, and these factors then combine to produce the overall cell architecture. By examining how these parameters are controlled in specific cell biological examples we can identify a handful of simple design principles that seem to underlie cellular architecture and assembly.
Self-organizing process
A process by which a set of components that can, inprinciple, be connected in various possible patterns will spontaneously associate into a limited subset of patterns, without any external input of information. ‘Selforganization’ is to be contrasted with ‘self-assembly’, in which components can only fit together such that only one pattern is possible.

Cilium
A microtubule-based motile and sensory organelle that projects from the surface of manyeukaryotic cells.

Flagellum
An alternative term for cilia when applied to eukaryotic cells.

Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, California 94158, USA. e‑mails: susanne.rafelski@ucsf.edu; wmarshall@biochem.ucsf.edu doi:10.1038/nrm2460

Cells are highly complex structures1. This complexity affects biologicalfunctions at many size scales2. But how does this complexity arise? What mechanisms pattern the architecture of the cell and where does the informa­ tion to specify a distinct architecture for different cell types come from? The amount of information that is needed to direct the action of the cellular assembly pathways could be mini­ mal because cellular morphogenesis is a self-organizing process3.Subject to simple inputs that can bias how the system develops, self­organizing processes can generate complex, patterned responses. In principle, therefore, the cell architecture could be specified by a small number of distinct genes, which would serve to modulate the inher­ ent self­organizing processes that lead to the physical shape of cells and organelles. Understanding the origins of cellorganization thus requires us to answer the ques­ tion of how the self­organizing physical and biochemical properties of cellular constituents can convert simple temporal changes in gene­expression levels into complex changes in physical, three­dimensional structures. This review addresses this question at the structural level of the organelle by asking how the geometry (the size, number, positionand morphology) of organelles is specified and regulated. In all cases, we will attempt to identify design principles by which a simple input containing minimal information can produce a complex output in terms of morphological changes. In engineering terminology a design principle is a simple rule that, when followed in the design of a machine, ensures or at least increases the likelihood ofproper assembly and function. We note that our use of the term does not imply the existence of a ‘designer’, but given the current interest in synthetic biology we suggest that the design principles used in evolution could now be

used to reprogramme cells in a rational way. For example, we argue that a common strategy used by cells to regulate organelle size is to limit either the assembly ordisassem­ bly rate of an organelle by a process that is inherently dependent on organelle size. Other specific principles that we discuss are the control of organelle number by the balance of organelle formation and partitioning; the establishment of cellular polarity by self­organization that is biased by external inputs; the control of organelle posi­ tion by direct motion on polarized cytoskeletal...