Effects of bursty synthesis in organelle biogenesis.

A fundamental question of cell biology is how cells control the number of organelles. The processes of organelle biogenesis, namely de novo synthesis, fission, fusion, and decay, are inherently stochastic, producing cell-to-cell variability in organelle abundance. In addition, experiments suggest that the synthesis of some organelles can be bursty. We thus ask how bursty synthesis impacts intracellular organelle number distribution. We develop an organelle biogenesis model with bursty de novo synthesis by considering geometrically distributed burst sizes. We analytically solve the model in biologically relevant limits and provide exact expressions for the steady-state organelle number distributions and their means and variances. We also present approximate solutions for the whole model, complementing with exact stochastic simulations. We show that bursts generally increase the noise in organelle numbers, producing distinct signatures in noise profiles depending on different mechanisms of organelle biogenesis. We also find different shapes of organelle number distributions, including bimodal distributions in some parameter regimes. Notably, bursty synthesis broadens the parameter regime of observing bimodality compared to the 'non-bursty' case. Together, our framework utilizes number fluctuations to elucidate the role of bursty synthesis in producing organelle number heterogeneity in cells.

Effects of length-dependent positive feedback on length distributions of microtubules undergoing hydrolysis.

Despite a rapid turnover of subunits, how cells control the lengths of cytoskeletal filaments (such as microtubules) is a fundamental question in cell biology. Here, we theoretically investigate how microscopic processes affect the length distributions of multiple microtubules growing stochastically in a shared subunit pool. In particular, we consider length-dependent positive feedback on filament growth and the chemical conversion from GTP-tubulin to GDP-tubulin (hydrolysis) inside a filament. We found different dynamical regimes for a single filament by simulating a model of microtubule kinetics, where both bimodal and unimodal (bell-shaped) length distributions emerge in the steady state. More significantly, the length distributions of multiple filaments were not unimodal, predicting a collective effect for more than one filament. Interestingly, when length distributions were bimodal, we also observed bistable toggling of individual lengths. Therefore, regulation of biophysical parameters (e.g., hydrolysis rate and feedback strength) can lead to length diversity in an ensemble of multiple microtubules.

Effects of random hydrolysis on biofilament length distributions in a shared subunit pool.

The sizes of filamentous structures in a cell are often regulated for many physiological processes. A key question in cell biology is how such size control is achieved. Here, we theoretically study the length distributions of multiple filaments, growing by stochastic assembly and disassembly of subunits from a limiting subunit pool. Importantly, we consider a chemical switching of subunits (hydrolysis) prevalent in many biofilaments like microtubules (MTs). We show by simulations of different models that hydrolysis leads to a skewed unimodal length distribution for a single MT. In contrast, hydrolysis can lead to bimodal distributions of individual lengths for two MTs, where individual filaments toggle stochastically between bigger and smaller sizes. For more than two MTs, length distributions are also bimodal, although the bimodality becomes less prominent. We further show that this collective phenomenon is connected with the nonequilibrium nature of hydrolysis, and the bimodality disappears for reversible dynamics. Consistent with earlier theoretical studies, a homogeneous subunit pool, without hydrolysis, cannot control filament lengths. We thus elucidate the role of hydrolysis as a control mechanism on MT length diversity.