Project description:Increasing cell size drives changes to the proteome, which affects cell physiology. As cell size increases, some proteins become more concentrated while others are diluted. As a result, the state of the cell changes continuously with increasing size. In addition to these proteomic changes, large cells have a lower growth rate (protein synthesis rate per unit volume). That both the cell's proteome and growth rate change with cell size suggests they may be interdependent. To test this, we used quantitative mass spectrometry to measure how the proteome changes in response to the mTOR inhibitor rapamycin, which decreases the cellular growth rate and has only a minimal effect on cell size. We found that large cell size and mTOR inhibition, both of which lower the growth rate of a cell, remodel the proteome in similar ways. This suggests that many of the effects of cell size are mediated by the size-dependent slowdown of the cellular growth rate. For example, the previously reported size-dependent expression of some senescence markers could reflect a cell's declining growth rate rather than its size per se. In contrast, histones and other chromatin components are diluted in large cells independently of the growth rate, likely so that they remain in proportion with the genome. Finally, size-dependent changes to the cell's growth rate and proteome composition are still apparent in cells continually exposed to a saturating dose of rapamycin, which indicates that cell size can affect the proteome independently of mTORC1 signaling. Taken together, our results clarify the dependencies between cell size, growth, mTOR activity, and the proteome remodeling that ultimately controls many aspects of cell physiology.
Project description:Data from nearly 1000 species reveal the upper bound to rates of biomass production achievable by natural selection across the Tree of Life. For heterotrophs, maximum growth rates scale positively with organism size in bacteria but negatively in eukaryotes, whereas for phototrophs, the scaling is negligible for cyanobacteria and weakly negative for eukaryotes. These results have significant implications for understanding the bioenergetic consequences of the transition from prokaryotes to eukaryotes, and of the expansion of some groups of the latter into multicellularity.
Project description:Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L-lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 μm(2). The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth.
Project description:Cellular populations in both nature and the laboratory are composed of phenotypically heterogeneous individuals that compete with each other resulting in complex population dynamics. Predicting population growth characteristics based on knowledge of heterogeneous single-cell dynamics remains challenging. By observing groups of cells for hundreds of generations at single-cell resolution, we reveal that growth noise causes clonal populations of Escherichia coli to double faster than the mean doubling time of their constituent single cells across a broad set of balanced-growth conditions. We show that the population-level growth rate gain as well as age structures of populations and of cell lineages in competition are predictable. Furthermore, we theoretically reveal that the growth rate gain can be linked with the relative entropy of lineage generation time distributions. Unexpectedly, we find an empirical linear relation between the means and the variances of generation times across conditions, which provides a general constraint on maximal growth rates. Together, these results demonstrate a fundamental benefit of noise for population growth, and identify a growth law that sets a "speed limit" for proliferation.
Project description:The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling. TORC2-dependent control of ceramide signaling strongly influences both cell size and growth rate. Thus, cells that cannot make ceramides fail to modulate their growth rate or size in response to changes in nutrients. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is embedded in a feedback loop that controls TORC2 signaling and helps set the level of TORC2 signaling to match nutrient availability. Together, the data suggest a model in which growth rate and cell size are mechanistically linked by ceramide-dependent signals arising from the TORC2 network.
Project description:Yeast cells, like mammalian cells, enlarge steadily as they age. Unabated cell growth can promote cellular senescence; however, the significance of the relationship between size and cellular lifespan is not well understood. Herein, we report a genetic link between cell size, growth rate and lifespan. Mutations that increase cell size concomitantly increase growth rate and decrease lifespan. As a result, large cells grow, divide and age dramatically faster than small cells. Conversely, small cell mutants age slowly and are long-lived. Investigation of the mechanisms involved suggests that attainment of a maximal size modulates lifespan. Indeed, cumulative results revealed that life expectancy is size-dependent, and that the rate at which cells age is determined in large part by the amount of cell growth per generation.
Project description:The processes involved in cell growth are extremely complicated even for a single cell organism such as Escherichia coli, while the relationship between growth rate and cell size is simple. We aimed to reveal the systematic link between them from the aspect of the genome-scale metabolic network. Since the growth rate reflects metabolic rates of bacteria and the cell size relates to phospholipid synthesis, a part of bacterial metabolic networks, we calculated the cell length from the cardiolipin synthesis rate, where the cardiolipin synthesis reaction is able to represent the phospholipid metabolism of Escherichia coli in the exponential growth phase. Combined with the flux balance analysis, it enables us to predict cell length and to examine the quantitative relationship between cell length and growth rate. By simulating bacteria growing in various nutrient media with the flux balance analysis and calculating the corresponding cell length, we found that the increase of the synthesis rate of phospholipid, the cell width, and the protein fraction in membranes caused the increase of cell length with growth rate. Different tendencies of phospholipid synthesis rate changing with growth rate result in different relationships between cell length and growth rate. The effects of gene deletions on cell size and growth rate are also examined. Knocking out the genes, such as Δ tktA, Δ tktB, Δ yqaB, Δ pgm, and Δ cysQ, affects growth rate largely while affecting cell length slightly. Results of this method are in good agreement with experiments.
Project description:Little is known about the factors driving within species Genome Size (GS) variation. GS may be shaped indirectly by natural selection on development and adaptative traits. Because GS variation is particularly pronounced in maize, we have sampled 83 maize inbred lines from three well described genetic groups adapted to contrasted climate conditions: inbreds of tropical origin, Flint inbreds grown in temperate climates, and Dent inbreds distributed in the Corn Belt. As a proxy for growth rate, we measured the Leaf Elongation Rate maximum during nighttime (LERmax) as well as GS in all inbred lines. In addition we combined available and new nucleotide polymorphism data at 29,090 sites to characterize the genetic structure of our panel. We found significant variation for both LERmax and GS among groups defined by our genetic structuring. Tropicals displayed larger GS than Flints while Dents exhibited intermediate values. LERmax followed the opposite trend with greater growth rate in Flints than in Tropicals. In other words, LERmax and GS exhibited a significantly negative correlation (r = - 0.27). However, this correlation was driven by among-group variation rather than within-group variation-it was no longer significant after controlling for structure and kinship among inbreds. Our results indicate that selection on GS may have accompanied ancient maize diffusion from its center of origin, with large DNA content excluded from temperate areas. Whether GS has been targeted by more intense selection during modern breeding within groups remains an open question.
Project description:Adaptation to local resource availability depends on responses in growth rate and nutrient acquisition. The growth rate hypothesis (GRH) suggests that growing fast should impair competitive abilities for phosphorus and nitrogen due to high demand for biosynthesis. However, in microorganisms, size influences both growth and uptake rates, which may mask trade-offs and instead generate a positive relationship between these traits (size hypothesis, SH). Here, we evolved a gradient of maximum growth rate (μmax) from a single bacterium ancestor to test the relationship among μmax, competitive ability for nutrients and cell size, while controlling for evolutionary history. We found a strong positive correlation between μmax and competitive ability for phosphorus, associated with a trade-off between μmax and cell size: strains selected for high μmax were smaller and better competitors for phosphorus. Our results strongly support the SH, while the trade-offs expected under GRH were not apparent. Beyond plasticity, unicellular populations can respond rapidly to selection pressure through joint evolution of their size and maximum growth rate. Our study stresses that physiological links between these traits tightly shape the evolution of competitive strategies.