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Jeffrey T. Nechleba

Publications and source records attributed to Jeffrey T. Nechleba.

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Statistical properties and dynamics of phenotype components in individual bacteria

Cellular phenotype is characterized by different components such as cell size, protein content and cell cycle time. These are global variables that are the outcome of multiple internal microscopic processes. Accordingly, they display some universal statistical properties and scaling relations, such as distribution collapse and relation between moments. Cell size statistics and its relation to growth and division has been mostly studied separately from proteins and other cellular variables. Here we present experimental and theoretical analyses of these phenotype components in a unified framework that reveals their correlations and interactions inside the cell. We measure these components simultaneously in single cells over dozens of generations, quantify their correlations, and compare population to temporal statistics. We find that cell size and highly expressed proteins have very similar dynamics over growth and division cycles, which result in parallel statistical properties, both universal and individual. In particular, while distribution shapes of fluctuations along time are common to all cells and components, other properties are variable and remain distinct in individual cells for a surprisingly large number of generations. These include temporal averages of cell size and protein content, and the structure of their auto-correlation functions. We explore possible roles of the different components in controlling cell growth and division. We find that in order to stabilize exponential accumulation and division of all components across generations, coupled dynamics among them is required. Finally, we incorporate effective coupling within the cell cycle with a phenomenological mapping across consecutive cycles, and show that this model reproduces the entire array of experimental observations.

q-bio.CB

Individuality and slow dynamics in bacterial growth homeostasis

Microbial growth and division are fundamental processes relevant to many areas of life science. Of particular interest are homeostasis mechanisms, which buffer growth and division from accumulating fluctuations over multiple cycles. These mechanisms operate within single cells, possibly extending over several division cycles. However, all experimental studies to date have relied on measurements pooled from many distinct cells. Here, we disentangle long-term measured traces of individual cells from one another, revealing subtle differences between temporal and pooled statistics. By analyzing correlations along up to hundreds of generations, we find that the parameter describing effective cell-size homeostasis strength varies significantly among cells. At the same time, we find an invariant cell size which acts as an attractor to all individual traces, albeit with different effective attractive forces. Despite the common attractor, each cell maintains a distinct average size over its finite lifetime with suppressed temporal fluctuations around it, and equilibration to the global average size is surprisingly slow (> 150 cell cycles). To demonstrate a possible source of variable homeostasis strength, we construct a mathematical model relying on intracellular interactions, which integrates measured properties of cell size with those of highly expressed proteins. Effective homeostasis strength is then influenced by interactions and by noise levels, and generally varies among cells. A predictable and measurable consequence of variable homeostasis strength appears as distinct oscillatory patterns in cell size and protein content over many generations. We discuss the implications of our results to understanding mechanisms controlling division in single cells and their characteristic timescales

q-bio.CB