Biological adhesion is the fundamental process where cells physically stick to each other or to the non-cellular material surrounding them, known as the Extracellular Matrix (ECM). Mediated by specialized surface proteins, this mechanism transforms individual cells into a cohesive, organized, multicellular organism. Adhesion is the underlying force responsible for tissue formation, structural integrity, and regulated communication between cells.
Molecular Components of Adhesion
Cell adhesion begins at the molecular level, mediated by specialized proteins called Cell Adhesion Molecules (CAMs). These molecules are broadly categorized into four main families, each with distinct functions and binding preferences. CAM interactions actively transmit signals into the cell.
Integrins are heterodimeric receptors composed of alpha and beta subunits. They function primarily as the cell’s anchor, linking the internal cytoskeleton to the external environment, specifically the Extracellular Matrix. Integrins are capable of bidirectional signaling, communicating information about the matrix into the cell and transmitting internal signals outward to adjust binding strength.
Cadherins are calcium-dependent glycoproteins that are the primary mediators of cell-to-cell binding between neighboring cells. They typically engage in homophilic adhesion, where a cadherin molecule on one cell binds to an identical cadherin molecule on an adjacent cell. The calcium requirement stabilizes the protein, which is necessary for their strong adhesive function.
Selectins mediate temporary cell-to-cell adhesion, playing a specialized role in the circulatory system. Unlike integrins and cadherins, selectins bind to specific carbohydrate structures on the surface of other cells in a calcium-dependent manner. This low-affinity binding allows cells, particularly immune cells, to slow down and “roll” along the inner walls of blood vessels before making a firm attachment.
The Immunoglobulin Superfamily of CAMs (IgSF CAMs) includes a large group of structurally diverse molecules. Examples include N-CAMs, which are prominent in the nervous system for axon guidance and neural connections, and ICAMs and VCAMs, which are important in immune cell interactions. These CAMs mediate both homophilic and heterophilic binding, often working in concert with other adhesion molecules.
Adhesion and Tissue Architecture
The collective action of adhesion molecules results in specialized structures called cell junctions, which physically connect and organize cells into functional tissues. These junctions are tailored to the specific mechanical and permeability needs of the tissue, such as the epithelial layers that line organs. Cell junctions are broadly classified into anchoring, occluding, and communicating types.
Anchoring junctions provide mechanical strength by tethering the cell’s internal cytoskeleton to either a neighboring cell or the surrounding matrix. Adherens junctions use Cadherins to connect the actin filament networks of adjacent cells, forming a continuous belt that helps coordinate cell shape changes. Desmosomes utilize specialized cadherins to anchor cells together via intermediate filaments, providing high tensile strength to tissues frequently under mechanical stress, like the skin and heart muscle.
Occluding junctions, known as tight junctions, form a seal between epithelial cells, blocking the passage of molecules and ions between cells. These junctions, composed of proteins like Claudins and Occludins, create a selective barrier that forces substances to pass through the cell itself rather than leaking around it. Tight junctions are also responsible for establishing cell polarity by separating the apical (top) surface from the basolateral (bottom) surface.
The Extracellular Matrix (ECM) provides the scaffolding upon which cells build and maintain tissues. It is a complex network of macromolecules, including fibrous proteins like collagen, elastic fibers, and hydrated gels formed by proteoglycans. Cells anchor themselves to this scaffolding primarily through Integrin receptors, forming structures called focal adhesions or hemidesmosomes. This anchorage maintains the tissue’s overall shape and integrity, providing physical support and resistance to compression.
Adhesion in Dynamic Biological Processes
Beyond maintaining static structure, adhesion is a dynamic process regulated during active biological functions. The ability to rapidly engage, strengthen, or break adhesive bonds is necessary for processes involving cell movement and interaction. This control is often achieved through internal signaling that changes the conformation and binding strength of the CAMs.
Immune surveillance relies on a sequence of precise adhesive interactions to allow white blood cells to exit the bloodstream and reach sites of inflammation. This process begins with the low-affinity binding of Selectins to carbohydrates on the blood vessel wall, causing the immune cell to roll. The cell then receives signals that activate its Integrin molecules, leading to firm adhesion to the vessel lining before the cell can squeeze through the wall into the tissue.
Cell migration, a necessary part of wound healing, development, and tissue remodeling, requires cells to disassemble and reassemble their ECM adhesions. Cells like fibroblasts, which migrate to repair a cut, use Integrins to grip the ECM in the direction of movement, while simultaneously releasing their rear-end adhesions. This coordinated breakdown and reformation of attachments allows the cell to pull itself forward across the tissue substrate.
The dysregulation of adhesion molecules is central to several pathological conditions, most notably cancer metastasis. For a primary tumor cell to spread, it must first lose its normal cell-to-cell adhesion, a process often linked to the down-regulation of Cadherins. Once detached, the cancer cell uses Integrins to navigate and adhere to new ECM environments, enabling it to travel through the body and form secondary tumors. Adhesion molecules are also exploited by many pathogens, which use them as receptors to bind to and infect host cells.