#integrin

Foot Down

Dotted around on the inner surface of our cells, focal adhesions act like tiny 'feet', but how they sense the floor is still a little mysterious. In this mammalian cell, scientists use their own sensors to snoop on what’s going on using super-resolution microscopy. One sensor sticks to a molecule called integrin on the underside of the cell, stretching as it wriggles to release tiny bursts of light (red dots). The speckled pattern suggests clusters of integrin may determine where focal adhesions form inside the cell – seen as clusters of tiny bone-like actin filaments in the cell’s cytoskeleton (yellow showing the filaments closest to the underlying surface, blue furthest away). Researchers might aim to exploit this mechanical link between neighbouring molecules inside and outside cells to guide their movement in health and disease.

Written by John Ankers

Image from work by Thomas Schlichthaerle and Caroline Lindner, and Ralf Jungmann

Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, Munich, Germany

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, May 2021

Making Contact

In multicellular organisms, fundamental processes enabling cells to grow, move and communicate rely on connections between cells and their environment, known as the extracellular matrix. Membrane proteins called integrins are critical to linking cells to this matrix, but they themselves need to associate with another protein, talin, in order to be active. Researchers have only recently uncovered the specific mechanisms behind this process: talin binds to lipids [fat] in the cell membrane, causing structural changes that reveal a previously-hidden site, which then contacts integrin. In cells with talin mutants lacking their membrane-binding portion (pictured, with the cytoskeleton protein actin in pink, and cell nuclei in blue), talin (in green) accumulates in the centre of the cell rather than moving to the membrane, and connections with the extracellular matrix are compromised. As processes requiring integrin are involved in cancer progression, a better understanding of talin’s role could suggest new therapeutic approaches.

Written by Emmanuelle Briolat

Image from the Izard laboratory, Scripps Research

Cell Adhesion Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA

Image copyright held by the original authors

Research published in PNAS, October 2018

Guided Growth

When you cut yourself, your body rushes to grow new skin over the wound. And a similar thing happens when internal injuries occur: an influx of new cells develop, with the guidance of a microscopic scaffolding system called the extracellular matrix, which fills the space between cells. However, this matrix can’t help when the injury is in the brain, like a stroke. Researchers add substances to act as artificial replacements for the matrix, but cells often have trouble keeping hold of these, and new structures tend to be leaky and flimsy. But a new injectable gel can help support more stable blood vessels, such as those pictured forming around a stroke site 10 days after treatment. It’s equipped with a substance that binds to integrin – the molecule that generally joins cells to the extracellular matrix. With this helping hand to hold, brain repair following stroke may be within our reach.

Written by Anthony Lewis

Image from the Segura Lab, UCLA

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, USA

Image copyright held by the original authors

Research published in Nature Materials, August 2017

You can see a lot by looking - a little bit of fluorescence microscopy to brighten your day. #microscopy #phdlife @academicchatter

Back in the lab post COVID and Dr Lee Troughton has been on the confocal microscope grabbing some cool pics of corneal epithelial keratinocytes assembling cell to matrix adhesions.

Most of these images are of hemidesomosome proteins (integrin b4, collagen XVII, BPAG1e) or laminin 332. Hemidesmosomes are the points of attachment for where sheets of epithelia attach to the non-cellular…

Have you ever thought about how cells migrate? At the theoretical level, movement of cells requires the conversion of stored chemical energy into mechanical energy. Though actin polymerization produces a force, which can be transmitted through the plasma membrane to integrins, the actual role of this transmission relative to cellular movement was unknown.

SBGrid member Timothy Springer and other researchers have been working to better understand how this actin polymerization plays a role in integrin activation in order to connect the molecular events to cellular migration for T cells. In order to study integrin activity, they used a fluorescent tension-sensing form of integrin. Consequently, the researchers were able to quantitatively determine that tension and integrin activity are linked and that the activation of integrin depends on actin polymerization within the cell. In short, actin polymerization within T cells produces tension within the beta-2 subunit, causing the activation of integrin. Since integrin is bound to extracellular ligands, this allows T cells to migrate in a highly coordinated manner using complex cellular mechanisms.

Publication date: Source:Journal of Molecular Biology, Volume 425, Issue 17 Author(s): Roman Bonet , Ioannis Vakonakis , Iain D. Campbell

Graphical abstract