Robustness and Universality in Organelle Size Control.

One of the grand challenges in cellular biophysics is understanding the precision with which cells assemble and maintain subcellular structures. Organelle sizes, for example, must be flexible enough to allow cells to grow or shrink them as environments demand yet be maintained within homeostatic limits. Despite identification of molecular factors that regulate organelle sizes we lack insight into the quantitative principles underlying organelle size control. Here we show experimentally that cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship we predict theoretically, our framework suggests that organelles grow in random bursts from a limiting pool of building blocks. Burstlike growth provides a general biophysical mechanism by which cells can maintain on average reliable yet plastic organelle sizes.

Single-cell analysis of habituation in Stentor coeruleus.

Although learning is often viewed as a unique feature of organisms with complex nervous systems, single-celled organisms also demonstrate basic forms of learning. The giant ciliate Stentor coeruleus responds to mechanical stimuli by contracting into a compact shape, presumably as a defense mechanism. When a Stentor cell is repeatedly stimulated at a constant level of force, it will learn to ignore that stimulus but will still respond to stronger stimuli. Prior studies of habituation in Stentor reported a graded response, suggesting that cells transition through a continuous range of response probabilities. By analyzing single cells using an automated apparatus to deliver calibrated stimuli, we find that habituation occurs via a single step-like switch in contraction probability within each cell, with the graded response in a population arising from the random distribution of switching times in individual cells. This step-like response allows Stentor behavior to be represented by a simple two-state model whose parameters can be estimated from experimental measurements. We find that transition rates depend on stimulus force and also on the time between stimuli. The ability to measure the behavior of the same cell to the same stimulus allowed us to quantify the functional heterogeneity among single cells. Together, our results suggest that the behavior of Stentor is governed by a two-state stochastic machine whose transition rates are sensitive to the time series properties of the input stimuli.