Behaviors of microtubules depend on two critical concentrations

Abstract

The concept of critical concentration (CC) is central to understanding behaviors of microtubules and other cytoskeletal polymers. Traditionally, these polymers are understood to have one CC, measured multiple ways and assumed to be the subunit concentration necessary for polymer assembly. However, this framework does not incorporate dynamic instability (DI), and there is work indicating that microtubules have two CCs. We use our previously established simulations to confirm that microtubules have (at least) two experimentally relevant CCs and to clarify the behaviors of individuals and populations relative to the CCs. At free subunit concentrations above the lower CC (CCIndGrow), growth phases of individual filaments can occur transiently; above the higher CC (CCPopGrow), the populations polymer mass will increase persistently. Our results demonstrate that most experimental CC measurements correspond to CCPopGrow, meaning \"typical\" DI occurs below the concentration traditionally considered necessary for polymer assembly. We report that [free tubulin] at steady state does not equal CCPopGrow, but instead approaches CCPopGrow asymptotically as [total tubulin] increases and depends on the number of stable microtubule seeds. We show that the degree of separation between CCIndGrow and CCPopGrow depends on the rate of nucleotide hydrolysis. This clarified framework helps explain and unify many experimental observations.