Illustration of cells migrating with tension forces highlighted.

Cell Migration: How Cells Detach to Move Faster

"New research reveals the mechanics behind cell movement, showing how cells use tension to detach and accelerate migration, impacting wound healing and immunity."


Cell migration is a fundamental process crucial for various biological functions, including immunity, development, and wound healing. Cells must efficiently move to perform these roles, requiring a delicate balance between adhesion and de-adhesion. While the mechanisms driving cell protrusion at the leading edge are well-understood, how cells detach at the trailing edge to facilitate movement has remained less clear.

Previous studies suggested that cells might biochemically regulate integrin de-adhesion, especially in less motile cells. However, highly motile cells like keratocytes, capable of rapid migration, require a more efficient detachment mechanism. A plausible alternative is the mechanical dissociation of integrin-ligand bonds via cellular force.

New research has successfully mapped integrin tension in migrating cells, revealing how cells concentrate force at the rear margin to detach and accelerate movement. This article delves into these findings, explaining the critical role of mechanical forces in cell migration and its broader implications for health and disease.

Integrin Tension: The Key to Cellular De-adhesion

Illustration of cells migrating with tension forces highlighted.

The study employed an integrative tension sensor (ITS) to measure integrin tension in migrating keratocytes. This sensor converts molecular tension into a fluorescent signal, enabling direct mapping of integrin tension with high resolution and sensitivity. The experiments revealed a critical insight: high-level integrin tension (HIT), ranging from 50-100 pN, is exclusively generated at the cell rear margin during cell migration.

Further analysis showed that this high-level integrin tension is not just present but actively involved in detaching the cell. Co-imaging of HIT and focal adhesions (FAs) demonstrated that HIT is produced to mechanically peel off FAs that lag behind, with HIT intensity directly correlated to the local cell retraction rate. This mechanical detachment contrasts with purely biochemical processes and highlights the force-driven nature of rapid cell migration.

  • Integrin tension, mapped with a tension sensor, is concentrated at the cell's rear.
  • High-level integrin tension (HIT) measures between 50-100 pN.
  • HIT mechanically peels off focal adhesions (FAs) to facilitate cell retraction.
To confirm the general role of HIT in cell de-adhesion, researchers induced artificial cell front retraction using hypertonic medium. This manipulation consistently generated HIT at retraction sites, reinforcing the idea that concentrating force at the cell margin is a universal mechanism for de-adhesion. Moreover, experiments with biotinylated keratocytes migrating via biotin-streptavidin bonds (instead of integrins) still exhibited HIT at the rear margin, demonstrating the cell's inherent ability to focus force for detachment, regardless of the adhesion mechanism.

Implications and Future Directions

This research provides compelling evidence that migrating keratocytes mechanically mediate cell rear de-adhesion by concentrating integrin tension. This mechanical regulation is crucial for rapid cell migration, offering a more efficient detachment mechanism than purely biochemical processes.

While this study focused on keratocytes, which exhibit rapid migration rates, the findings may not directly apply to all cell types. Further research is needed to investigate whether similar mechanisms are at play in cells with lower motility. Understanding the nuances of cell-specific de-adhesion strategies could reveal new therapeutic targets for various conditions.

Future studies could explore the interplay between mechanical and biochemical signals in regulating cell de-adhesion. Investigating how cells integrate these signals to fine-tune their migratory behavior will provide a more comprehensive picture of cell migration and its role in health and disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.isci.2018.11.016, Alternate LINK

Title: Keratocytes Generate High Integrin Tension At The Trailing Edge To Mediate Rear De-Adhesion During Rapid Cell Migration

Subject: Multidisciplinary

Journal: iScience

Publisher: Elsevier BV

Authors: Yuanchang Zhao, Yongliang Wang, Anwesha Sarkar, Xuefeng Wang

Published: 2018-11-01

Everything You Need To Know

1

What is cell migration and why is it important?

Cell migration is a fundamental process for various biological functions, including immunity, development, and wound healing. Cells must efficiently move to perform these roles. Efficient cell movement requires a delicate balance between adhesion and de-adhesion. The process is crucial for enabling cells to reach sites of injury or infection, participate in developmental processes, and maintain tissue homeostasis.

2

What is high-level integrin tension (HIT) and what is its role in cell movement?

High-level integrin tension (HIT) is the mechanical force, ranging from 50-100 pN, generated at the rear margin of migrating cells, specifically keratocytes. This force is crucial for detaching the cell from its environment. Researchers used an integrative tension sensor (ITS) to map this HIT, which directly correlates with the cell's retraction rate. The cell uses HIT to mechanically peel off focal adhesions (FAs) that lag behind. The application of HIT is a mechanical process that is used to facilitate rapid cell migration.

3

How does integrin tension facilitate cell movement?

Integrin tension is the mechanical force cells use to detach and move. In the context of cell migration, particularly in rapidly migrating cells like keratocytes, integrin tension plays a critical role in rear de-adhesion. The study used an integrative tension sensor (ITS) to map integrin tension. The research showed that high-level integrin tension (HIT) is generated at the rear margin of the cells, mechanically detaching focal adhesions (FAs).

4

What are focal adhesions (FAs) and how does high-level integrin tension (HIT) affect them?

Focal adhesions (FAs) are the points where cells adhere to their environment. In the context of rapid cell migration, the study showed that high-level integrin tension (HIT) mechanically peels off these FAs at the rear margin of the cells. This mechanical detachment is crucial for the cell's ability to retract and move forward, facilitating efficient cell migration. This force-driven mechanism contrasts with biochemical processes, highlighting the importance of mechanical forces in cellular movement.

5

What are the broader implications of this research on cell de-adhesion?

The study's findings suggest that concentrating force at the cell margin is a universal mechanism for cell de-adhesion. Furthermore, it offers insights into potential therapeutic targets for improving wound healing and modulating immune responses. Since cell migration is involved in a wide range of biological processes, understanding the mechanisms involved in cell movement is essential. This knowledge provides a foundation for developing treatments for diseases that involve impaired cell migration.

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