Artwork: Dan Nowakowski/Nicholas Taylor
The bacterial flagellar engine has an automatic gearshift
Navish Wadhwa
Harvard University
Machines perform specific tasks for us
Cells use molecular machines for specific tasks
ATP synthase
Ribosome
Replisome
Do cells have smart machines too?
Yes, they do.
We use the bacterium E. coli as a model organism
Inhabits guts of mammals
Some strains are harmful, most harmless
Multiple flagella per cell
Bacteria are the smallest self-propelled swimmers
Many bacteria swim by rotating helical flagella
Slowed down 20 times
Reversal of flagellar rotation enables changes in the swimming direction
A nanoscale motor powers flagellar rotation
Changes in the rotor enable bidirectional rotation
Torque production differs between CCW and CW
Automatic gearshift in cars allows the engine to adapt to changing terrains
Automatic gearshift in E. coli allows the motor to adapt to changing loads
What is the physical and molecular mechanism underlying this automatic gearshift?
How can we change motor load?
Instantaneously
Reversibly
Controllably
Electrorotation allows full control on motor load
Instantaneous
Reversible
Controllable
Electrorotation allows full control on motor load
A change in load triggers stepwise changes in motor speed
The stator remodels in response to load change
Wadhwa et al., PNAS, 2019
Lele et al., PNAS, 2013
Nord et al., PNAS, 2017
Remodeling kinetics vary with electrorotation speed
Higher electrorotation speed leads to lower torque
Hypothesis
Stator remodeling depends on torque
A quantitative model for stator assembly
We extracted the on rate ($k_+$) and the off rate ($k_-$) from the data
The off-rate decreases with torque
Free energy of the bound state decreases with torque
The off-rate decreases exponentially with torque
Molecular mechanism for torque-dependent unbinding rate
Low torque
High torque
Torque anisotropy allows us to test the model
Collapse of CCW and CW data validates the model
Conclusions and perspective
Cars and bacteria use different approaches
Cars adapt the transmission while bacteria adapt the engine itself
What is the ecological relevance of autonomous motor remodeling?
Credit: Eshel Ben-Jacob and Ingham Colin
Acknowledgements
Collaborators
Howard Berg (Harvard)
Yuhai Tu (IBM)
Rob Phillips (Caltech)
Ethan Garner (Harvard)
Nicholas Taylor (U. Copenhagen)
Marc Erhardt (Humboldt U.)
Alberto Sassi (IBM)
K99/R00: GM134124
References:
Wadhwa, Tu, and Berg, 2021, PNAS 118 (15) e2024608118.
Santiveri, Roa-Eguiara, Kühne, Wadhwa, Hu, Berg, Erhardt, and Taylor, 2020, Cell 183 (1) 244 - 257.
Wadhwa, Phillips, and Berg, 2019, PNAS 116 (24) 11764-11769.
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