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Published on: March 8, 2017
Cyclic mechanical reinforcement of integrin-ligand interactions
Fang Kong1, Zhenhai Li, William M Parks
1Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Molecular Cell
|February 19, 2013
Summary
Cyclic mechanical forces strengthen cell adhesion by reinforcing fibronectin-integrin bonds. This "cyclic mechanical reinforcement" enhances bond longevity and stability, revealing a new mechanism for cell-matrix interactions.
Area of Science:
- Cell biology
- Biophysics
- Biochemistry
Background:
- Cells dynamically regulate adhesion through integrins, which link the extracellular matrix to the cytoskeleton.
- Integrins serve as mechanical anchorages and signaling platforms, crucial for cellular functions.
- Cellular adhesion is influenced by both internal and external forces.
Purpose of the Study:
- To investigate the effect of cyclic mechanical forces on fibronectin-integrin α5β1 bond stability.
- To elucidate the phenomenon of "cyclic mechanical reinforcement" in cell adhesion.
- To identify the molecular mechanisms underlying force-induced strengthening of receptor-ligand interactions.
Main Methods:
- Application of cyclic forces to fibronectin-integrin α5β1 bonds.
- Measurement of bond lifetimes under varying force conditions.
- Analysis of the roles of specific binding sites (RGD, synergy) and integrin domains.
Main Results:
- Cyclic forces transformed short-lived (1s) fibronectin-integrin α5β1 bonds into long-lived (100s) states.
- This phenomenon, termed "cyclic mechanical reinforcement," showed memory of force history and accumulated over cycles.
- Strengthening involved the RGD binding site, facilitated by the synergy site, and required a flexible integrin hybrid domain.
Conclusions:
- Cyclic mechanical forces can significantly enhance and stabilize cell adhesion through a reinforcement mechanism.
- This study reveals a novel pathway for mechanical regulation of integrin-ligand interactions.
- Identified molecular components critical for cyclic force-mediated cell adhesion strengthening.
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In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
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01:13Cell-matrix's Response to Mechanical Forces
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01:26Tension Response at Adherens Junctions
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01:03Anchoring Junctions
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