Vimentin undergoes liquid–liquid phase separation to form droplets which wet and stabilize actin fibers

A Arkaprabha Basu (Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University) T Tommy Krug (Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University) B Benjamin du Pont (Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University) Q Qiaoling Huang (Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University) S Sijie Sun (Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University) S Stephen A. Adam (Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University) R Robert D. Goldman (Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University) D David A. Weitz

Abstract

The cytoskeleton is composed of F-actin, microtubules, and intermediate filaments (IFs). Vimentin is one of the most ubiquitous and well-studied IFs. It is involved in many activities including wound healing, tissue fibrosis, and cancer metastasis, all of which require rapid vimentin IF assembly. In this paper, we report that vimentin forms liquid condensates which appear to enable rapid filament growth. Given the transient nature of these droplets, we focus on properties of vimentin-Y117L, which has a point mutation that leads to formation of condensates but not IFs, enabling us to study these droplets in detail. The droplets dissolve under 1,6-Hexanediol treatment and under decreasing concentration, confirming that they are liquid, and phase separated. These condensates extensively wet actin stress fibers, rendering them resistant to actin-binding drugs and protecting them from depolymerization. We show similar behavior occurs in wild-type vimentin during its assembly into filaments.

Article Details

Volume / Issue Vol. 122, Issue 10
Published March 11, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (8)

A

Arkaprabha Basu

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

T

Tommy Krug

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

B

Benjamin du Pont

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

Q

Qiaoling Huang

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

S

Sijie Sun

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University

S

Stephen A. Adam

Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University

R

Robert D. Goldman

Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University

D

David A. Weitz