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Related Concept Videos

Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
Mechanical Protein Functions01:58

Mechanical Protein Functions

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
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.
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

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Related Experiment Video

Updated: Jun 26, 2026

Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
14:16

Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium

Published on: February 11, 2009

Structural basis for selectin mechanochemistry.

Timothy A Springer1

  • 1Immune Disease Institute, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, WAB Room 250, Boston, MA 02115, USA. springer@idi.harvard.edu

Proceedings of the National Academy of Sciences of the United States of America
|January 2, 2009
PubMed
Summary
This summary is machine-generated.

Tensile force on selectin-ligand complexes shifts them to a high-affinity state. This mechanical force-induced allostery explains selectin-mediated cell adhesion and leukocyte rolling.

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Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
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Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

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Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
14:16

Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium

Published on: February 11, 2009

Adhesion Frequency Assay for In Situ Kinetics Analysis of Cross-Junctional Molecular Interactions at the Cell-Cell Interface
13:22

Adhesion Frequency Assay for In Situ Kinetics Analysis of Cross-Junctional Molecular Interactions at the Cell-Cell Interface

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Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

Area of Science:

  • Biochemistry and Molecular Biology
  • Cellular and Molecular Mechanics
  • Immunology

Background:

  • Selectins are crucial adhesion molecules mediating leukocyte rolling on vessel walls under hydrodynamic forces.
  • Selectins exhibit distinct high-affinity (liganded) and low-affinity (unliganded) conformations, differing in domain orientation.
  • Understanding the structural basis of selectin mechanochemistry is vital for deciphering immune cell trafficking.

Purpose of the Study:

  • To investigate how tensile force influences the conformation of selectin-ligand complexes in vivo.
  • To elucidate the allosteric mechanisms by which mechanical force is transmitted through selectin domains.
  • To explain the structural basis of selectin-mediated mechanochemistry and leukocyte rolling adhesion.

Main Methods:

  • Analysis of crystal structures of liganded and unliganded selectins.
  • Computational modeling to examine force transmission across selectin domains.
  • Identification of key residues and interfaces involved in force-induced conformational changes.

Main Results:

  • Tensile force applied to selectin-ligand complexes favors a more extended, high-affinity conformation.
  • Allosteric signaling from the EGF-lectin interface to the ligand-binding site involves a 'prybar' mechanism.
  • Force-induced disruption of interfaces at switch regions (switch1, switch2, switch3) and EGF domain residues underlies conformational changes.

Conclusions:

  • Mechanical force acts as a regulator of selectin affinity, favoring high-affinity states.
  • The identified allosteric pathways and force-transducing elements explain selectin mechanochemistry.
  • Understanding these mechanisms provides insight into leukocyte adhesion and inflammatory responses.