Cells adhere to each other and the extracellular matrix through adhesion molecules: cadherins mediate calcium-dependent, homophilic cell-cell contacts and are critical for tissue integrity; integrins are heterodimeric receptors that bind matrix proteins (collagen, fibronectin, laminin) and couple the matrix to the cytoskeleton. Adhesion is not passive; signals from the matrix (through integrins) and cell-cell contacts (through cadherins) regulate gene expression, cell survival, and proliferation. Loss of adhesion is a hallmark of metastatic cancer; restoration of adhesion is a goal of therapeutic intervention.
From your understanding of cell migration, you know that cells interact physically with their surroundings through integrin-based focal adhesions and cytoskeletal dynamics. Cell adhesion builds on this concept: rather than just enabling movement, adhesion molecules create the stable connections that hold tissues together and allow cells to communicate with their neighbors and the extracellular matrix. Without adhesion, a tissue would be nothing more than a bag of loose cells.
The two major families of adhesion molecules serve different purposes. Cadherins are cell-to-cell adhesion proteins that require calcium ions to function — remove the calcium, and cadherin bonds fall apart, which is why the chelating agent EDTA is used to dissociate tissues in the lab. Cadherins are homophilic, meaning E-cadherin on one cell binds to E-cadherin on an adjacent cell. Different tissues express different cadherins: epithelial cells express E-cadherin, neural cells express N-cadherin, and this differential expression is one mechanism by which cells of the same type find and stick to each other during development, a phenomenon called cell sorting. On the intracellular side, cadherins connect to the actin cytoskeleton through adaptor proteins called catenins (α-, β-, and p120-catenin), creating a continuous mechanical link from one cell's cytoskeleton through the adhesion junction to the next cell's cytoskeleton.
Integrins handle cell-to-matrix adhesion. They are heterodimers — each composed of one α and one β subunit — and their particular combination determines which matrix protein they bind (collagen, fibronectin, laminin, and others). A remarkable feature of integrins is bidirectional signaling. In "outside-in" signaling, binding to the extracellular matrix triggers intracellular signaling cascades through focal adhesion kinase (FAK) that regulate cell survival, proliferation, and gene expression. In "inside-out" signaling, intracellular signals change the integrin's conformation from a bent, low-affinity state to an extended, high-affinity state, allowing the cell to rapidly modulate its grip on the matrix. This is how a circulating white blood cell, initially non-adhesive, can quickly latch onto an inflamed blood vessel wall.
The importance of adhesion becomes starkly visible in disease. In metastatic cancer, tumor cells typically downregulate E-cadherin (often through a process called epithelial-mesenchymal transition), loosening their connections to neighboring cells and enabling them to invade surrounding tissue and enter the bloodstream. Conversely, genetic defects in integrins cause diseases like leukocyte adhesion deficiency, where immune cells cannot adhere to blood vessel walls and therefore cannot reach sites of infection. These examples illustrate that adhesion is not merely structural glue — it is an active signaling system that tells cells where they are, whether they should survive, and how they should behave.