Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Monday Speaker Abstracts

Intrinsic and Extrinsic Noise in an Organelle Size Control System Wallace Marshall University of California, San Francisco, CA, USA No Abstract

Cell-size Determination by the Bacterial Actin Cytoskeleton Kerwyn C. Huang . Stanford, Stanford, CA, USA.

Changes in bacterial cell size are associated with critical changes in fitness and growth rate at the single-cell level; at the population level, these changes affect biofilm formation and virulence. To explore the relationships among genotype, structural phenotype, and bacterial physiology, we constructed a library of Escherichia coli mutants with a range of cell sizes and used fluorescence-activated cell sorting to identify subtle changes in cell shape, allowing us to query the effect of cell shape on several physiological behaviors, growth rate, DNA content, and drug sensitivity. The quantitative relationships revealed by this strategy highlight the complex and dynamic links between bacterial morphology and physiology. In E. coli , the actin-like protein MreB localizes in a curvature-dependent manner and spatially coordinates cell-wall insertion to maintain cell shape across changing environments, although the molecular mechanism by which cell width is regulated remains unknown. I will show that the bitopic protein RodZ regulates the biophysical properties of MreB and alters the spatial organization of E. coli cell-wall growth. The relative expression levels of MreB and RodZ changed in a manner commensurate with variations in growth rate and cell width. We carried out molecular dynamics simulations and single-cell analyses to determine that RodZ alters the curvature-based localization of MreB, and therefore cell shape. Together, our results show that E. coli controls its shape and dimensions by differentially regulating RodZ and MreB to alter the patterning of cell-wall insertion, highlighting the rich regulatory landscape of cytoskeletal molecular biophysics.

26