Date of Completion

9-4-2013

Embargo Period

9-4-2013

Keywords

rod-shaped, bacteria, peptidoglycan, gram-negative, gram-positive, cell wall, shape

Major Advisor

Ann Cowan, PhD

Co-Major Advisor

Charles Wolgemuth, PhD

Associate Advisor

Ji Yu, PhD

Associate Advisor

Michael Blinov, PhD

Associate Advisor

William Mohler, PhD

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Rod-shaped bacteria grow in length without changing their width [1, 2]. A major feature of bacterial cell growth is the remodeling of the cell wall, the primary structure giving the bacterium its shape and structural integrity. In many rod-shaped bacteria, the process by which the cell wall gets larger as the cell grows involves severing bonds that link the existing cell wall material together in order to insert and bind new material. Coordination between severing and insertion is likely necessary in order to prevent the cell wall from rupturing due to the large pressure difference between the inside and outside of the cell. As more bacteria are becoming resistant to antibiotics, which typically target cell wall synthesis, understanding the regulatory mechanisms involved in bacterial growth and morphology may provide new paradigms for treating infections. Although there have been many hypotheses proposed about the mechanisms underlying the regulation of cell width, the actual process by which bacteria grow and maintain their shape remains unclear [3, 4].

To begin to address this question, we developed a simple mechanochemical model explaining the dependence of cell length and degree of crosslinking on the replication rate of rod-shaped bacteria [5]. In this model we observed that faster growing cells are less crosslinked and longer in length than slower growing cells, as has been experimentally measured. Since our model predicts that faster growing cells have weaker cell walls, a prediction of the model is that the fractional change in length of a cell upon osmotic shock should be greater for faster growing cells. We tested this prediction and found good agreement between the model and experiments. Finally, in order to understand the consequences of crosslinking fraction and glycan strand length on the elastic properties of the cell wall, we developed a 2D percolation model of the peptidoglycan meshwork. By simulating the effects of a given stress on this network, we were able to define a constitutive relationship for the cell wall as a function of crosslink fraction and glycan strand length. This model allows us to observe how mechanical and biochemical properties can affect cell shape.

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