Elsevier

Current Opinion in Cell Biology

Volume 68, February 2021, Pages 20-27
Current Opinion in Cell Biology

The principles of cellular geometry scaling

https://doi.org/10.1016/j.ceb.2020.08.013Get rights and content

Abstract

Cellular dimensions profoundly influence cellular physiology. For unicellular organisms, this has direct bearing on their ecology and evolution. The morphology of a cell is governed by scaling rules. As it grows, the ratio of its surface area to volume is expected to decrease. Similarly, if environmental conditions force proliferating cells to settle on different size optima, cells of the same type may exhibit size-dependent variation in cellular processes. In fungi, algae and plants where cells are surrounded by a rigid wall, division at smaller size often produces immediate changes in geometry, decreasing cell fitness. Here, we discuss how cells interpret their size, buffer against changes in shape and, if necessary, scale their polarity to maintain optimal shape at different cell volumes.

Introduction

Cell morphogenesis is a fundamental, systems-level process in which cells attain their characteristic size and shape. Cellular dimensions impact on nutrient exchange, ion and water fluxes, cytoskeletal organization, intracellular transport, diffusion, and cortical patterning [1,2]. During cell growth, its surface area-to-volume ratio is expected to decrease according to the two-thirds power law function [3]. The direct consequence of differential scaling between the cell surface and volume is a potential for size-dependent variation in cellular processes. This problem can be solved by proliferation, with growing cells dividing at some defined optimal size. Yet, proliferating cells routinely settle on different size optima in response to nutrient availability and other environmental factors. Depending on cellular geometry, this may impose the need for a mechanism that scales cell shape to new size at division. Cells may also require specialized strategies to stabilize their surface-to-volume ratio, including cell shape alterations or restructuring endomembrane compartments [3]. Such scaling phenomena are widespread in biology [2,3] but the underlying mechanisms remain largely elusive. In this review, we examine the geometric implications of cellular size in free-living yeasts, which are largely autonomous in making their cell cycle decisions.

Cellular scaling in multicellular eukaryotes, where cells are subject to tissue and organismal control, and in prokaryotes has been discussed in several wonderful reviews [4, 5, 6, 7, 8]. The quantitative theory explaining different geometric scaling strategies has been advanced by Jordan Okie [3] in a fascinating and accessible paper.

Section snippets

Scaling of gene expression may constrain growth to control maximum cell size

In proliferating cell populations, the maximum cell size inherent to specific conditions depends on coordination of cell growth with division [9]. The rule is simple: a mother cell doubles in size and divides into two daughters. Cell size homeostasis is usually robust for each cell type and growth condition [8, 9, 10∗∗]. How achieving a certain size commits cell to an entry into the next cell cycle has been the subject of lively debate even in the case of established cell cycle models, such as

Gene expression can be scaled up to a point

Size-dependent scaling of expression output is possible until genes are fully saturated with the transcriptional machinery [19]. The synthetic capacity of the genome thus sets the maximum cell size compatible with fitness, which in the case of proliferating cells includes their ability to reproduce. It is instructive to look at the outcomes of cellular growth unrestrained by division. When prevented from entering the next cell cycle, growing budding and fission yeasts eventually reach the stage

Cells can interpret their geometry to cue division

A reverse situation — when protein content is allowed to increase in the absence of cellular volume expansion — leads to subsequent ‘supergrowth’ in the fission yeast Schizosaccharomyces pombe (S. pombe) [22]. The rate of cell expansion returns to normal once cytoplasmic density is normalized, suggesting the operation of homeostatic mechanisms coordinating protein biosynthesis with an increase in the cell surface area. Curiously, these very rapidly growing cells are subject to normal size

Cell size and shape are regulated by the environment

The growth, and hence, the maximum cell size is modulated by nutrients and other environmental conditions [31, 32, 33, 34]. This evolutionarily conserved response that advances the commitment to the next cell cycle presumably allows cells to maximize proliferation under nutrient limitation and, if necessary, exit the replicative cell cycle. This does not have to present a geometric problem for cells with budding division patterns, which can simply limit the extent of growth in the daughter

Does (polarized) growth control scaling?

The fact that S. japonicus efficiently scales its geometry to cell size can perhaps explain why it can do with a single division site positioning mechanism — but why would it be different from its cousin S. pombe? It appears that at least part of the answer could be the sheer differences in the cellular growth rate, which is three times higher for S. japonicus [51]. Haploid S. pombe actually does scale, something that has been previously overlooked in the field. For instance, the cellular

Concluding remarks

Understanding the rules governing a fundamental relationship between cellular size and shape can be greatly facilitated by integrating mechanistic cell biological studies with comparative and/or evolutionary analyses. For instance, some marine yeasts exhibit alternating budding/fission division cycles [66], and S. japonicus, which normally divides symmetrically, undergoes asymmetric cell division during scaling [51]. This suggests that budding (asymmetric) and fission (symmetric) cell division

Conflict of interest statement

Nothing declared.

Acknowledgements

The authors are grateful to R. Mori, F. Uhlmann and S. Marguerat for discussions and E. Makeyev for suggestions on the manuscript. Their work is supported by a Wellcome Trust Senior Investigator Award (103741/Z/14/Z) and BBSRC project grant (BB/T000481/1) to SO.

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