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Cell Syst. 2016 Jun 22;2(6):402-11. doi: 10.1016/j.cels.2016.05.006. Epub 2016 Jun 16.

Mechanical Genomics Identifies Diverse Modulators of Bacterial Cell Stiffness.

Author information

1
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
2
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
3
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
4
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
5
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: kchuang@stanford.edu.
6
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: weibel@biochem.wisc.edu.

Abstract

Bacteria must maintain mechanical integrity to withstand the large osmotic pressure differential across the cell membrane and wall. Although maintaining mechanical integrity is critical for proper cellular function, a fact exploited by prominent cell-wall-targeting antibiotics, the proteins that contribute to cellular mechanics remain unidentified. Here, we describe a high-throughput optical method for quantifying cell stiffness and apply this technique to a genome-wide collection of ∼4,000 Escherichia coli mutants. We identify genes with roles in diverse functional processes spanning cell-wall synthesis, energy production, and DNA replication and repair that significantly change cell stiffness when deleted. We observe that proteins with biochemically redundant roles in cell-wall synthesis exhibit different stiffness defects when deleted. Correlating our data with chemical screens reveals that reducing membrane potential generally increases cell stiffness. In total, our work demonstrates that bacterial cell stiffness is a property of both the cell wall and broader cell physiology and lays the groundwork for future systematic studies of mechanoregulation.

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