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Lubensky, D. K.

Publications and source records attributed to Lubensky, D. K..

4 recordsLinked to original sources

Growth, metabolism, and the benefits of clock-enabled anticipation

Circadian clocks are found in myriad species across the tree of life. They are commonly assumed to provide a selective advantage by enabling organisms to anticipate daily environmental changes. It has proven remarkably difficult, however, to move beyond this general idea to explain precisely what advantage anticipation confers and to quantify how large this benefit is. Here, we address these challenges by developing a mathematical model of diurnally varying growth and metabolism in the cyanobacterium Synechococcus elongatus, which fixes carbon through photosynthesis during the day and stores a portion of it as glycogen for use during the night. Specifically, we extend the framework introduced by Hwa and coworkers (Scott et al., Science 330, 1099 (2010)), which quantifies the relationship between growth and proteome composition, to a circadian context. We find that the fastest growth is achieved when glycogen production during the day is minimized to the amount required to sustain essential nighttime processes; growth then occurs exclusively during the day, in agreement with experimental observations. However, the slow relaxation of the proteome, arising from the intrinsically slow growth rate of S. elongatus, severely constrains the implementation of this optimal strategy: In the absence of anticipation, the cell must grow at night in order to produce proteins essential for nighttime metabolism. In contrast, with anticipation enabled by a circadian clock, the bacterium can instead adjust its proteome late in the day, allowing it to avoid less efficient nighttime growth altogether, thereby significantly enhancing its growth rate.

microbiology↗

Generation of fate patterns via intercellular forces

Studies of fate patterning during development typically emphasize cell-cell communication via diffusible signals. Recent experiments on monolayer stem cell colonies, however, suggest that mechanical forces between cells may also play a role. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony boundary, more contractile than cells at the center, seed a pattern that propagates via force transmission. In agreement with previous observations, our model implies that the width of the outer fate domain depends only weakly on colony diameter. We further predict and confirm experimentally that this same width varies non-monotonically with substrate stiffness. This finding supports the idea that mechanical stress can mediate patterning in a manner similar to a morphogen; we argue that a similar dependence on substrate stiffness can be achieved by a chemical signal only if strong constraints on the signaling pathways mechanobiology are met.

biophysics↗

Defect patterns on the curved surface of fish retinae suggest mechanism of cone mosaic formation

The outer epithelial layer of zebrafish retinae contains a crystalline array of cone photoreceptors, called the cone mosaic. As this mosaic grows by mitotic addition of new photoreceptors at the rim of the hemispheric retina, topological defects, called \"Y-Junctions\", form to maintain approximately constant cell spacing. The generation of topological defects due to growth on a curved surface is a distinct feature of the cone mosaic not seen in other well-studied biological patterns like the R8 photoreceptor array in the Drosophila compound eye. Since defects can provide insight into cell-cell interactions responsible for pattern formation, we characterize the arrangement of cones in individual Y-Junction cores as well as the spatial distribution of Y-junctions across entire retinae. We find that for individual Y-junctions, the distribution of cones near the core corresponds closely to structures observed in physical crystals. In addition, Y-Junctions are organized into lines, called grain boundaries, from the retinal center to the periphery. In physical crystals, regardless of the initial distribution of defects, grain boundaries can form via the mobility of individual particles. By imaging in live fish, we demonstrate that grain boundaries in the cone mosaic instead appear during initial mosaic formation, without requiring defect motion. Motivated by this observation, we show that a computational model of repulsive cell-cell interactions generates a mosaic with grain boundaries. In contrast to paradigmatic models of fate specification in mostly motionless cell packings, this study emphasizes the role of cell motion, guided by cell-cell interactions during differentiation, in forming biological crystals. Such a route to the formation of regular patterns may be especially valuable in situations, like growth on a curved surface, where long-ranged, elastic, effective interactions between defects can help to group them into grain boundaries.\n\nAUTHOR SUMMARYFrom hair cells in the mammalian inner ear to the bristles on a flys back, sensory cells often form precise arrays, ensuring that these cells are evenly spread out on the tissues surface. Here we consider the zebrafish cone mosaic, a crystal of cone photoreceptors in the outer retinal layer. Because the cone mosaic grows from the rim of the curved retinal surface, new rows of cones (i.e., defects) are inserted to maintain constant spacing between sensory cells. We study the spatial distribution of these defects to gain insight into how the cone pattern forms. By imaging retinae in live fish, we find that as differentiating cones are incorporated into the mosaic, defects form lines (grain boundaries) that separate mostly defect-free domains. Then, we show that a computational model based on repulsion between mobile cells during their incorporation into the mosaic generates similar grain boundaries. This study thus suggests that cell motion governed by repulsive cell-cell interactions can play an important role in establishing regular patterns in living systems.

biophysics↗

The statistics of noisy growth with mechanical feedback in elastic tissues

Tissue growth is a fundamental aspect of development and is intrinsically noisy. Stochasticity has important implications for morphogenesis, precise control of organ size, and regulation of tissue composition and heterogeneity. Yet, the basic statistical properties of growing tissues, particularly when growth induces mechanical stresses that can in turn affect growth rates, have received little attention. Here, we study the noisy growth of elastic sheets subject to mechanical feedback. Considering both isotropic and anisotropic growth, we find that the density-density correlation function shows power law scaling. We also consider the dynamics of marked, neutral clones of cells. We find that the areas (but not the shapes) of two clones are always statistically independent, even when they are adjacent. For anisotropic growth, we show that clone size variance scales like the average area squared and that the mode amplitudes characterizing clone shape show a slow 1/n decay, where n is the mode index. This is in stark contrast to the isotropic case, where relative variations in clone size and shape vanish at long times. The high variability in clone statistics observed in anisotropic growth is due to the presence of two soft modes--growth modes that generate no stress. Our results lay the groundwork for more in-depth explorations of the properties of noisy tissue growth in specific biological contexts.

biophysics↗