Structual Visualization of Cytoskeletal Force Tranduction

Author

Ayala Carl

Date of Award

2023

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Alushin Laboratory

Abstract

Cells adhere to their surroundings, mechanically interfacing their intracellular actin cytoskeletons with their local extracellular environments. This enables contractile forces generated by myosin motors to mediate transduction of mechanical cues into biochemical signaling pathways by unclear mechanisms.In this thesis, I show that myosin forces elicit conformational transitions in actin filaments (F-actin) that modulate interactions between F-actin and the force-activated cell adhesion protein α-catenin.In vitro reconstitution and cryo-electron microscopy reveal myosin force-evoked superhelical F-actin spirals. Three-dimensional reconstruction and variability analysis uncover extensive asymmetric remodeling of F-actin’s helical lattice. This is recognized by α-catenin, which cooperatively binds along individual strands, preferentially engaging interfaces featuring extended inter-subunit distances while simultaneously suppressing rotational deviations to regularize the lattice.Collectively,I find that myosin forces can deform F-actin, generating a conformational landscape that is detected and reciprocally modulated by α-catenin,providing a direct structural glimpse at force transduction through the cytoskeleton.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for The degree of Doctor of Philosophy

Recommended Citation

Carl, Ayala, "Structual Visualization of Cytoskeletal Force Tranduction" (2023). Student Theses and Dissertations. 766.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/766