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:

Machines perform specific tasks for us

Cells use molecular machines to perform specific tasks

ATP synthase



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

Turner et al., J. Bacteriol., 2000

Bacteria are the smallest self-propelled swimmers

Many bacteria swim by rotating helical flagella

Slowed down 20 times

Turner et al., J. Bacteriol., 2000

A nanoscale motor powers
swimming in bacteria

Motor torque depends upon its rotation speed

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

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?




Electrorotation allows
full control over motor load




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

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

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

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

Wadhwa et al., PNAS, 2021

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.


Howard Berg (Harvard)

Yuhai Tu (IBM)

Rob Phillips (Caltech)

Alberto Sassi (IBM)

NIH Pathway to Independence Award