Cell adhesion is fundamental to the formation and function of complex organisms, enabling individual cells to connect with each other and their surroundings. This network of connections allows for the development of tissues and organs with specialized functions. Two major families of proteins, integrins and cadherins, manage these cellular interactions. While both are involved in adhesion, they operate in distinct ways, binding to different partners and playing separate roles in maintaining the body’s architecture.
Integrins and the Extracellular Matrix
Integrins are transmembrane proteins that act as bridges between a cell’s internal environment and the world outside it. Structurally, they are heterodimers, meaning each is composed of two distinct protein chains, an alpha (α) and a beta (β) subunit. There are 18 known α subunits and 8 β subunits in vertebrates, which can combine to form 24 different integrin receptors, each with specific binding capabilities. This modular design allows for a wide range of functions tailored to different cell types.
The primary role of integrins is to connect the cell’s internal cytoskeleton to the extracellular matrix (ECM). The ECM is a meshwork of proteins and carbohydrates, such as collagen and fibronectin, that surrounds cells and provides structural support for tissues. By anchoring the cell to this external framework, integrins provide stability and allow cells to sense and respond to mechanical forces.
This connection is not static; integrins are dynamic structures that can form and break their attachments to the ECM. This capability is important for cell migration, where a cell repeatedly grips the matrix, pulls itself forward, and then releases its hold to move. Integrins facilitate this “crawling” motion, which is necessary for tissue development, immune responses, and wound healing.
Cadherins and Cell-to-Cell Junctions
While integrins manage a cell’s relationship with its external scaffold, cadherins specialize in mediating direct connections between adjacent cells. These transmembrane proteins are the main components of cell junctions that hold tissues together, such as the epithelial layers lining organs. The name “cadherin” is derived from “calcium-dependent adhesion,” highlighting a defining feature. Its extracellular portion contains repeating domains that require calcium ions to bind, making the protein rigid and capable of forming a strong bond.
A characteristic of cadherin function is homophilic binding. This means cadherin molecules on one cell bind to identical cadherin molecules on a neighboring cell. This mechanism allows cells of the same type to recognize each other and sort into coherent tissues during embryonic development. For example, E-cadherin on epithelial cells ensures they stick tightly to form a continuous layer.
Inside the cell, the cytoplasmic tails of cadherins link to the cytoskeleton through proteins called catenins. This linkage couples the cytoskeletons of neighboring cells, creating a mechanically strong unit. This forms structures known as adherens junctions, which provide mechanical strength and maintain tissue integrity.
Key Distinctions in Function and Signaling
The primary difference between these proteins is their binding partners. Integrins mediate cell-matrix adhesion by binding to ECM components like fibronectin and collagen, forming focal adhesions. In contrast, cadherins are responsible for cell-cell adhesion through homophilic binding, creating adherens junctions. Furthermore, cadherin function is strictly dependent on calcium, a requirement not shared by integrins.
Their signaling pathways are also distinct. Integrins facilitate bidirectional “outside-in” and “inside-out” signaling. Outside-in signaling occurs when integrin binding to the ECM triggers internal chemical signals that influence cell survival, proliferation, and migration. Inside-out signaling allows the cell to control the binding affinity of its integrins in response to internal cues.
Cadherin-mediated signaling helps maintain tissue architecture and contact inhibition. Contact inhibition is a phenomenon that instructs cells to stop proliferating when they form a complete layer.
Implications in Health and Disease
The roles of integrins and cadherins are illustrated in cancer metastasis. For a tumor to spread, cancer cells must first break away from the primary tumor mass. This is often achieved by downregulating cadherins, particularly E-cadherin. The loss of these cell-cell adhesion molecules weakens the connections holding the tumor together, allowing individual cancer cells to detach and become mobile.
Once free, these cancer cells use integrins to navigate their escape. They use integrin-mediated adhesion to crawl through the surrounding extracellular matrix, invade nearby tissues, and enter blood or lymphatic vessels. The expression of certain integrins, like αvβ3, is often correlated with increased metastatic potential as they facilitate this invasive migration. After traveling to a distant site, the cancer cells use integrins again to exit the bloodstream and establish a new tumor.
A similar interplay is seen in wound healing. When skin is injured, epithelial cells at the wound edge must migrate to cover the exposed area. This process requires a temporary loosening of cadherin-based cell-cell junctions to allow for movement. Simultaneously, these cells upregulate integrins to grip the underlying ECM and pull themselves into the wound bed. Once the wound is covered, cadherin expression is restored, re-establishing the strong junctions needed to reform a cohesive epithelial barrier.