(4bw) Bacterial Mechanobiology: Rotary Flagellar Motors As Mechanosensors

Mechanobiology is an emerging area in biophysics, which focuses on how mechanical forces regulate complex biological processes in living systems. I am interested in determining the molecular mechanisms by which rotary flagellar motors transduce mechanical signals and trigger biochemical signaling and cell-differentiation in motile bacteria. Determining these signaling cascades will provide molecular insights into how bacteria adapt and survive in challenging environments, including how bacteria establish infections.

A majority of motile bacteria swim by rotating helical filaments with reversible, electric motors. Changes in the direction of rotation (switching) and speed of rotation are fundamental characteristics of the flagellar motor, critical for chemotaxis and motility. However, the biophysical mechanisms of relevant motor functions are unclear. In the Berg lab, I proposed a theoretical model predicting how motor protein exchange controls the switching function, and successfully tested the model through single molecule fluorescence measurements (1). Recently, I have discovered how the motor acts as a viscometer – it remodels the stator complex when triggered by mechanical stimuli (2). To our knowledge, this is the only known biological motor which varies the number of force-generating units to tailor its response to external mechanical loads. Importantly, these discoveries provide a handle on an important developmental problem: how do flagellar motors signal cell-development?

            My research program will focus on mechanobiology, in a variety of model prokaryotic systems, with emphasis on the physics of motility and self-assembly in biological macromolecules. These investigations might lead to the development of strategies to control microbial growth, based on targeting of the surface-sensing mechanisms in rotary motors.

[1]   P. P. Lele, R. W. Branch, V. Nathan, H. C. Berg, “Mechanism for adaptive remodeling of the bacterial flagellar switch”, Proc. Natl. Acad. Sci. USA (2012), 109 (49), 20018-20022.

[2]   P. P. Lele, Basarab G. Hosu, H. C. Berg, “Dynamics of mechanosensing in the bacterial flagellar motor”, under revision, Proc. Natl. Acad. Sci. USA.

Collaborators:

Prof. Urs Jenal, Biozentrum, University of Basel, Switzerland

Dr. Yuhai Tu, RSM & Manager, Theory & Computational Physics, IBM, USA