Scaling of subcellular actin structures with cell length through decelerated growth.

Shane G McInally,Jane Kondev,Bruce L Goode

doi:10.7554/elife.68424

Abstract

How cells tune the size of their subcellular parts to scale with cell size is a fundamental question in cell biology. Until now, most studies on the size control of organelles and other subcellular structures have focused on scaling relationships with cell volume, which can be explained by limiting pool mechanisms. Here, we uncover a distinct scaling relationship with cell length rather than volume, revealed by mathematical modeling and quantitative imaging of yeast actin cables. The extension rate of cables decelerates as they approach the rear of the cell, until cable length matches cell length. Further, the deceleration rate scales with cell length. These observations are quantitatively explained by a 'balance-point' model, which stands in contrast to limiting pool mechanisms, and describes a distinct mode of self-assembly that senses the linear dimensions of the cell.

Highlights

The size of a cell’s internal parts are scaled to its overall size
A popular model of cellular scaling is the limiting pool mechanism, wherein maintaining a constant concentration of molecular components enables the subcellular structure to increase in size proportionally with cell volume (Goehring and Hyman, 2012; de Godoy et al, 2008) This allows larger cells to assemble larger structures, since the total number of molecular building blocks increases proportionally with cell volume
Cells appear to use a limiting pool mechanism to scale the size of their nucleoli, centrosomes, and mitotic spindles (Hazel et al, 2013; Good et al, 2013; Weber and Brangwynne, 2015; Greenan et al, 2010; Decker et al, 2011; Lacroix et al, 2018)

Summary

Introduction

The size of a cell’s internal parts are scaled to its overall size. This size-scaling behavior has been demonstrated for organelles as well as large macromolecular assemblies, illustrating the broad importance of adapting the size of internal structures to the geometric dimensions of the cell (Rafelski et al, 2012; Levy and Heald, 2010; Hazel et al, 2013; Good et al, 2013; Weber and Brangwynne, 2015; Greenan et al, 2010; Jorgensen et al, 2007; Decker et al, 2011; Neumann and Nurse, 2007; Lacroix et al, 2018). Limiting pool models cannot explain how the size of a linear subcellular structure scales with the linear dimensions of a cell, rather than its volume These mechanisms predict that a two fold increase in the radius of a spherical cell will increase the length of a linear structure eight fold, following the eight fold increase in cell volume. In the boundary-sensing model, the assembly rate is greater than the disassembly rate until the extending cable physically encounters the rear of the cell, causing one or both rates to abruptly change (Figure 2C, and Figure 2—figure supplement 1A; Reber and Goehring, 2015) This model predicts that the cable extension rate will be constant until the cable tip encounters the back of the cell. The balance-point model requires that either the assembly rate, the disassembly rate, or both rates are length-dependent, and defines steady state cable length as the point at which these two rates are balanced

D Balance-point model

Materials and methods