Artwork: Dan Nowakowski/Nicholas Taylor
Mechano-adaptation in a large protein complex
Soft, Living, Active and Adaptive Matter (SLAAM) Seminar
November 2021
Navish Wadhwa
Harvard University
slides for this talk: WadhwaLab.com/talks
Machines perform specific tasks for us
Cells use molecular machines to perform 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
A nanoscale motor powers
swimming in bacteria
Motor torque depends upon its rotation speed
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 over motor load
Instantaneous
Reversible
Controllable
Electrorotation allows
full control over motor load
A change in load triggers stepwise changes in motor speed
The motor adapts to changes
in load by remodeling its stator
Remodeling kinetics depend on 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 outlook
Cars and bacteria use different approaches
Cars adapt the transmission while bacteria adapt the engine itself
Flagellar motor is a bacterial mechanosensor
Molecular machines are not static, fixed structures, but flexible, dynamic, and responsive.
Acknowledgements
Howard Berg (Harvard)
Yuhai Tu (IBM)
Rob Phillips (Caltech)
Alberto Sassi (IBM)
