Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Kinetic model for integrin-mediated adhesion release during cell migration.

S P Palecek1, A F Horwitz, D A Lauffenburger

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA. s-palecek@uchicago.edu

Annals of Biomedical Engineering
|April 13, 1999
PubMed
Summary

This study explores how cells detach from surfaces during migration. The researchers developed a mathematical model to understand how integrins, the cytoskeleton, and the extracellular matrix interact during rear retraction. The model predicts two detachment types: rapid at high forces or low adhesiveness, and slow at low forces or high adhesiveness. The amount of integrin left on the substratum indicates the detachment type. The model also explains why some cells, like leukocytes, move quickly while others, like fibroblasts, move more slowly. This work provides insights into the parameters that influence cell migration speed.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

GPS for QSP: A Summary of the ACoP6 Symposium on Quantitative Systems Pharmacology and a Stage for Near-Term Efforts in the Field.

CPT: pharmacometrics & systems pharmacology·2016
Same author

Systematic Analysis of Quantitative Logic Model Ensembles Predicts Drug Combination Effects on Cell Signaling Networks.

CPT: pharmacometrics & systems pharmacology·2016
Same author

Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

Mucosal immunology·2016
Same author

Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

Mucosal immunology·2016
Same author

Physiome-on-a-Chip: The Challenge of "Scaling" in Design, Operation, and Translation of Microphysiological Systems.

CPT: pharmacometrics & systems pharmacology·2015
Same author

Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.

CPT: pharmacometrics & systems pharmacology·2015

Area of Science:

  • Cell migration dynamics in biophysics
  • Integrin signaling in cell adhesion
  • Computational modeling of cellular processes

Background:

Cell migration is a complex process influenced by multiple factors, including the rate of detachment from the substratum. While it is known that rear retraction can limit migration speed, the mechanisms governing this process remain unclear. Prior research has shown that integrins play a key role in cell adhesion and signaling. However, the exact interplay between integrin-matrix interactions, cytoskeletal forces, and detachment dynamics has not been fully elucidated. This gap motivated the development of a mathematical framework to explore these relationships. The current study builds on existing knowledge of integrin function and introduces a novel approach to model detachment kinetics. By integrating biophysical and biochemical variables, the model aims to clarify how different conditions lead to distinct detachment behaviors. This work addresses a specific need to better understand the parameters that influence cell migration speed.

Purpose Of The Study:

Keywords:
cell migration dynamicsintegrin signalingcomputational modelingadhesion release mechanisms

Frequently Asked Questions

The model predicts rapid detachment at high forces or low adhesiveness and slow detachment at low forces or high adhesiveness.

Integrin clustering influences retraction kinetics by affecting the rate of integrin-matrix or integrin-cytoskeleton dissociation.

The amount of integrin extracted serves as an indicator of the detachment phenotype, distinguishing between rapid and slow detachment.

The model suggests that leukocytes detach rapidly and migrate quickly, while fibroblasts detach more slowly and release more integrins.

Related Experiment Videos

This study aimed to investigate how integrin-mediated adhesion release affects cell migration speed. The researchers sought to develop a mathematical model that captures the interactions between integrins, the cytoskeleton, and the extracellular matrix. The model was designed to predict how applied forces and integrin clustering influence rear retraction dynamics. By simulating different conditions, the study aimed to identify two distinct detachment phenotypes. The researchers also intended to explain why certain cell types detach more easily than others. This approach allows for a deeper understanding of the mechanisms governing cell movement. The model provides a framework for analyzing how adhesion strength and force application influence detachment rates. The ultimate goal was to delineate parameters that could be used to regulate cell speed in different detachment regimes.

Main Methods:

The researchers constructed a mathematical model to simulate integrin-mediated adhesion release. The model incorporates biophysical and biochemical interactions between integrins, the cytoskeleton, and the extracellular matrix. It examines how applied forces and integrin clustering influence retraction kinetics. The model uses computational simulations to predict detachment phenotypes under varying conditions. The researchers analyzed how high forces or low adhesiveness lead to rapid detachment. They also explored how low forces or high adhesiveness result in slower detachment. The model tracks the amount of integrin extracted from the cell rear as an indicator of detachment type. The simulations provide a framework for understanding how different parameters affect rear retraction and cell migration speed.

Main Results:

The model predicts two distinct detachment phenotypes based on force and adhesiveness. In the first, detachment is rapid and dominated by integrin-matrix dissociation at high forces or low adhesiveness. In the second, detachment is slower and dominated by integrin-cytoskeleton dissociation at low forces or high adhesiveness. The amount of integrin extracted from the cell rear serves as an assay for detachment type. During rapid detachment, cells leave little integrin on the substratum. During slow detachment, a large fraction of integrin rips from the membrane. The model identifies parameters that can be used to regulate cell speed in each regime. It also explains why some cell types detach easily while others do not. The simulations show that leukocytes and keratocytes exhibit rapid detachment, whereas fibroblasts show slower detachment. These findings suggest that detachment kinetics are influenced by both force and adhesiveness.

Conclusions:

The model provides a framework for understanding how integrin-mediated adhesion release influences cell migration speed. It predicts two distinct detachment phenotypes based on force and adhesiveness. Rapid detachment occurs at high forces or low adhesiveness and is dominated by integrin-matrix dissociation. Slow detachment occurs at low forces or high adhesiveness and is dominated by integrin-cytoskeleton dissociation. The amount of integrin extracted from the cell rear indicates the detachment type. The model identifies parameters that can be used to regulate cell speed in each regime. It also explains why some cell types detach easily while others do not. The simulations suggest that leukocytes and keratocytes exhibit rapid detachment, whereas fibroblasts show slower detachment. These findings align with the authors' hypothesis that detachment kinetics are influenced by both force and adhesiveness.

High forces or low adhesiveness lead to rapid detachment dominated by integrin-matrix dissociation.

The model identifies force and adhesiveness as key parameters that can be manipulated to regulate cell speed in each detachment regime.