Artwork: Dan Nowakowski/Nicholas Taylor


Autonomous mechano-adaptation in bacterial swimming motility

BPPB seminar
April 2022

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.

Many bacteria swim by rotating helical flagella

Slowed down 20X




Turner et al., J Bact 2000

A nanoscale motor powers
swimming in bacteria

How does the flagellar motor cope with changes in mechanical load?

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?

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

Wadhwa et al., PNAS 2019

The motor adapts to changes
in load by remodeling its stator


Wadhwa et al., PNAS 2019
Wadhwa et al., PNAS 2021

Remodeling kinetics depend on electrorotation speed

Wadhwa et al., PNAS 2019

Higher electrorotation speed leads to lower torque

Chen and Berg, Biophys J 2000

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


Nord et al., PNAS 2017
Wadhwa et al., PNAS 2019

The off-rate decreases with torque


Free energy of the bound state decreases with torque

The off-rate decreases exponentially with torque

Torque anisotropy allows us to test the model

Chen and Berg, Biophys J 2000
Yuan et al, PNAS 2010

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

Take home message


Future work: How do bacteria sense, process, and respond to their mechanical environment?

Openings for postdocs, gradaute students, technician, lab manager!

Acknowledgements


Howard C. Berg (1934 - 2021)


Rob Phillips (Caltech)


Yuhai Tu
(IBM)


Alberto Sassi (IBM)