Northwestern Medicine investigators have uncovered new details about cell-cell adhesion, identifying previously unknown subpopulations of molecules within junction structures that connect cells to their neighbors.
The investigators discovered that these junction structures – bundles made of actin filaments – have two different types of actin within them. This differentiation helps cell-cell adhesion be both strong and flexible, according to Sergey Troyanovsky, PhD, professor of Dermatology and of Cell and Developmental Biology, and senior author of the study published in Cell Reports.
“We think this is very important for the complex behavior of cells within tissue,” said Troyanovsky, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Cell-cell adhesion is an important basic mechanism in the body, where individual cells interact and attach to neighboring cells to form structures and organs within the body. These cell-cell junctions need to be strong to hold these structures together, but also require a high degree of flexibility, to allow for tissue readjustment during cell movement, cell proliferation and for other cells to pass by.
The actual bonding mechanism between most cells is accomplished with cadherin molecules which are transmembrane proteins located at the end of actin bundles that cluster together and link with other cadherin clusters in neighboring cells, forming a handshake bond between cells.
This process is extremely dynamic: Cadherin clusters form, bond with clusters in other cells and dissipate all within one second, and in the following second, other groups of cadherin go through the same process. This continual forming and dissipation of bonds is one reason these cell-cell junctions are flexible, according to Troyanovsky.
In the study, Troyanovsky and his collaborators examined the properties of actin bundles, identifying two separate populations of actin within them.
“They are differently organized and have very different dynamics,” Troyanovsky said.
One population of actin made up most of the bundles’ stalk and was extremely stable. The other population was found at the tip, upon which the cadherin clusters sat and was very dynamic — matching the fast-paced tempo of cadherin.
In one experiment, the investigators artificially slowed the formation and breaking apart of cadherin clusters, to see how the actin at the tip responded. Surprisingly, this actin population slowed down as well, showing how deeply integrated these processes are, according to Troyanovsky.
“We really should regard it as one mechanism,” Troyanovsky said. “The formation and disassociation of the clusters which always match the actin.”
Without this coordination, cell-cell junctions would break down at the first dynamic imbalance between cells, which would undermine structures and let cells move where they don’t belong, Troyanovsky said.
“The actin and cadherin synchronization is very important for allowing or not allowing cells to move freely between two adjacent cells,” he said.
Troyanovsky said that in future studies, he is interested in exploring how cadherin is involved in cell-to-cell signaling, and if these junction structures play a role in gatekeeping which cells are able to pass through.
The work was funded by the National Institutes of Health grants AR044016, AR070166 and GM062270, and the National Science Foundation grant MCB-1412472.