# Mechanometabolism of cell adhesion: Vinculin regulates bioenergetics via RhoA-ROCK

## TL;DR

This paper shows how the protein vinculin connects cell adhesion to energy use and migration, revealing a new way cells control movement through bioenergetics.

## Contribution

The study reveals a novel regulatory link between vinculin, RhoA/ROCK signaling, and cellular bioenergetics during migration.

## Key findings

- Vinculin knockout increases metabolic activity and Rho kinase-dependent cell shape changes.
- RhoA/Rho kinase activity enhances protrusions and energy production, linking adhesion to bioenergetics.
- Metabolic inhibition reduces blebbing protrusions, showing interdependence between energy and migration.

## Abstract

The focal adhesion protein vinculin affects the dynamics of the actin cytoskeleton, and reorganization of the actin cytoskeleton is an energetically demanding process important in cell migration. Here, Fabiano et al. establish a relationship between vinculin, cell bioenergetics, and migration behavior, and the RhoA/ROCK/myosin II pathway in MDA-MB-231 cells.

Cell migration and cytoskeletal remodeling are energetically demanding processes. Reorganizing the cytoskeleton requires ATP to fuel the actomyosin complex, enabling cells to adhere to and migrate through a matrix. While it is known that energy is required for cell migration, the mechanism by which cell–extracellular matrix adhesion influences cell energetics is unclear. Here, we investigated the relationship between cell–extracellular matrix adhesion and cellular metabolic state with a focus on vinculin given its role in connecting the cytoskeleton to focal adhesions and extracellular space. Knocking out vinculin increases the metabolic activity in cells and results in fast, frequent Rho kinase activity–dependent changes in cell shape and protrusions. The cellular protrusion dynamics and bioenergetics are interrelated processes, as stimulating RhoA/Rho kinase activity increases dynamic blebbing protrusions and energy production, and inhibiting metabolism decreases the frequency of blebbing cell protrusions. This link between cell–extracellular matrix adhesion and bioenergetics provides a novel basis by which cellular metabolism and cell migration could be controlled.