Artwork: DanĀ Nowakowski/Nicholas Taylor



Mechano-adaptation in a large protein complex

GRC Stochastic Physics in Biology, Ventura, CA


Navish Wadhwa

Harvard University

slides for this talk: WadhwaLab.com/talks

Acknowledgements


Howard Berg (Harvard)


Yuhai Tu (IBM)


Rob Phillips (Caltech)


Alberto Sassi (IBM)




K99/R00: GM134124

Many bacteria swim by rotating helical flagella

Slowed down 20 times




Turner et al., J. Bacteriol., 2000

A nanoscale motor powers flagellar rotation

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

Lele et al., PNAS, 2013

What is the physical and molecular mechanism underlying this automatic gearshift?

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

Wadhwa et al., PNAS, 2019

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

Wadhwa et al., PNAS, 2019

Higher electrorotation speed leads to lower torque




Hypothesis
Stator remodeling depends on torque

The off-rate decreases with torque


Wadhwa et al., PNAS, 2019

Collapse of CCW and CW data validates the model

Wadhwa et al., PNAS, 2021

Molecular mechanism for torque-dependent unbinding rate

Low torque

High torque

Conclusions and perspective





Evolution has given bacteria a remarkable molecular machine that is capable of autonomous mechano-adaptation.