Andrea Page-McCaw, a Stevenson Professor and specialist in cell and developmental biology at Vanderbilt University, was the principal investigator on a ground breaking study. This study has uncovered important new information about how the body senses and repairs damage to basement membranes. These thin sheets of extracellular matrix envelop and cushion just about every organ in the body. The study, co-led by recent Boothe graduate student Aubrie M. Stricker, was published in the journal Developmental Cell.
This study highlights the importance of local cells in patrolling basement membrane integrity. They do this by detecting mechanical rigidity. When the membranes experience trauma, their rigidity increases. This signals the surrounding cells to recruit a fresh army of highly specialized “matrix mender” cells that initiate the tissue repair process. This finding sheds light on a field of cellular biology that has remained largely under-studied. Prior to this inquiry, we had no idea how basement membranes were sensed and repaired.
Understanding Basement Membranes
Basement membranes are essential structural elements in tissue architecture, serving as supportive, anchoring structures to cells. They help to mediate cross-talk between different cellular layers and serve to improve the multilayered structure and function of organs. Though vital, researchers have been missing an overall picture of how these protective membranes react to injury.
Andrea Page-McCaw expressed her frustration regarding the knowledge gap in this field:
“Virtually nothing was known about how the damaged matrix is detected and repaired.”
This confusion led her team to further investigate what’s going on behind the scenes. The study looked specifically at how cells sense increased basement membrane stiffness after injury. This detection serves as the cue to swing into action, activating those crucial body fix-it functions.
Mechanisms of Detection and Repair
The novel experimental method by which the research team conducted their investigation was equally impressive, since they employed fruit flies as a model organism. Using cutting edge imaging techniques the researchers were able to get an unprecedented view of how local cells interact with the basement membrane. In addition, the surface view he was able to discern with these techniques provided key insights into how cells were communicating with their environments.
As researchers, one of the most fascinating discoveries they made through their investigation was… They found that cells employ a specialized “touch” sense to detect injuries to the basement membrane. When damage happens, particular signaling pathways are triggered, titled recruitment of matrix mender cells that aid in the repair process.
“Basement membranes lie outside cells, and we wanted to know how cells know when the membranes are damaged and how they get repaired.”
In her research, Aubrie M. Stricker found something surprising. In her postdoc, she figured out that Piezo, a mechanically activated ion channel, is very much needed for the development of these matrix mender cells. Page-McCaw described this moment as exhilarating:
This exciting finding opens entirely new avenues for understanding how mechanical signals drive cellular behaviors to facilitate tissue repair.
“It was a very exciting day when Aubrie discovered that Piezo is required for the matrix menders to appear.”
The collaborative spirit on the research that Page-McCaw pioneered at Vanderbilt University was very much a part of her research laboratory. She noted that support from colleagues across different disciplines played a pivotal role in advancing their findings:
Collaborative Research Efforts
This kind of interdisciplinary collaboration highlights the indispensable role of collaboration in scientific research, allowing for more holistic investigations into complex biological phenomena.
“Vandy has a highly collaborative atmosphere, and we were able to get help with automated image analysis from our colleague Shane Hutson.”
Such interdisciplinary collaboration underscores the importance of teamwork in scientific research, enabling more comprehensive investigations into complex biological phenomena.
