Speaker: Shane McInally, Brandeis

Title: Control of actin cable length by decelerated growth and network geometry

Abstract: The sizes of many subcellular structures are coordinated with cell size to ensure that these structures meet the functional demands of the cell. In eukaryotic cells, these subcellular structures are often membrane-bound organelles, whose volume is the physiologically important aspect of their size. Scaling organelle volume with cell volume can be explained by limiting pool mechanisms, wherein a constant concentration of molecular building blocks enables subcellular structures to increase in size proportionally with cell volume. However, limiting pool mechanisms cannot explain how the size of linear subcellular structures, such as cytoskeletal filaments, scale with the linear dimensions of the cell. Recently, we discovered that the length of actin cables in budding yeast (used for intracellular transport) precisely matches the length of the cell in which they are assembled. Using mathematical modeling and quantitative imaging of actin cable growth dynamics, we found that as the actin cables grow longer, their extension rates slow (or decelerate), enabling cable length to match cell length. Importantly, this deceleration behavior is cell-length dependent, allowing cables in longer cells to grow faster, and therefore reach a longer length before growth stops at the back of the cell. In addition, we have unexpectedly found that cable length is specified by cable shape. Our imaging analysis reveals that cables progressively taper as they extend from the bud neck into the mother cell, and further, this tapering scales with cell length. Integrating observations made for tapering actin networks in other systems, we have developed a novel mathematical model for cable length control that recapitulates our quantitative experimental observations. Unlike other models of size control, this model does not require length-dependent rates of assembly or disassembly. Instead, feedback control over the length of the cable is an emergent property due to the cross-linked and bundled architecture of the actin filaments within the cable. This work reveals a new strategy that cells use to coordinate the size of their internal parts with their linear dimensions. Similar design principles may control the size and scaling of other subcellular structures whose physiologically important dimension is their length.