Cell adhesion is the process by which cells connect and interact with each other or with the extracellular matrix, a network of molecules outside the cell. This fundamental mechanism is foundational in all multicellular organisms, forming the basis for the organization and function of tissues and organs. Without proper cell adhesion, the complex structures of living beings could not form or maintain their integrity.
The Molecular Basis of Cell Adhesion
Cell adhesion relies on specialized proteins on the cell surface, known as cell adhesion molecules (CAMs). These molecules facilitate physical connections between cells or between cells and their surroundings. There are four main classes of CAMs, each with distinct functions.
Cadherins
Cadherins are calcium-dependent CAMs that primarily mediate cell-to-cell adhesion. They engage in homophilic binding, where a cadherin molecule on one cell binds to the same type on an adjacent cell. E-cadherin, for example, is prevalent in epithelial tissues and plays a role in selective cell adhesion.
Integrins
Integrins are another class of CAMs that act as heterodimers, composed of alpha and beta subunits. Unlike cadherins, integrins mainly facilitate cell-to-extracellular matrix adhesion, connecting the cell’s internal cytoskeleton to components like collagen or fibronectin. They also transmit signals between the external environment and the cell’s interior, influencing cell growth and movement.
Selectins
Selectins are calcium-dependent CAMs that enable transient cell-to-cell interactions, particularly within the bloodstream. They bind to specific carbohydrate structures on opposing cell surfaces. L-selectin, E-selectin, and P-selectin are examples found on white blood cells, endothelial cells, and platelets, involved in the rolling and adhesion of immune cells to blood vessel walls.
Immunoglobulin (Ig) superfamily CAMs
Immunoglobulin (Ig) superfamily CAMs are a diverse group of proteins with extracellular domains similar to antibodies. These CAMs can mediate both homophilic and heterophilic adhesion, interacting with other Ig superfamily CAMs or integrins. Members like Intercellular Adhesion Molecules (ICAMs) and Vascular Cell Adhesion Molecule-1 (VCAM-1) have diverse roles, including neuronal patterning and immune responses.
How Cells Stick Together: Types of Adhesion
Cells use specialized junctions to achieve adhesion, providing different levels of strength. These junctions are broadly categorized into those that connect cells to other cells and those that connect cells to the extracellular matrix.
Cell-Cell Adhesion
Cell-cell adhesion often involves anchoring junctions, which provide mechanical strength and link the cytoskeletons of adjacent cells. Adherens junctions are belt-like structures that encircle cells and connect their actin filaments. These junctions utilize cadherin proteins to connect cells, contributing to tissue integrity.
Desmosomes
Desmosomes are spot-like junctions that rivet cells together, particularly in tissues subjected to mechanical stress, such as skin and cardiac muscle. They serve as anchoring sites for intermediate filaments, a type of cytoskeletal fiber, providing significant tensile strength to the cell sheet.
Tight Junctions
Tight junctions form continuous, belt-like seals around the perimeter of epithelial cells. This tight seal acts as a barrier, regulating the passage of molecules between cells and preventing the diffusion of membrane proteins.
Cell-Extracellular Matrix Adhesion
For cell-extracellular matrix adhesion, two primary types of anchoring junctions exist. Focal adhesions are dynamic, spot-like connections where integrins link the cell’s actin cytoskeleton to components of the extracellular matrix, such as fibronectins. These structures are involved in cell migration and signaling. Hemidesmosomes anchor the cell’s intermediate filaments to the basal lamina, providing strong attachment to underlying tissues.
Why Cell Adhesion Matters in the Body
Cell adhesion is fundamental to the proper functioning and maintenance of an organism, playing a role in numerous biological processes. A primary function is the organization and maintenance of tissues and organs. Cell adhesion ensures cells are correctly aligned and connected, forming stable structures like epithelial layers or organized muscle tissue.
Embryonic Development
During embryonic development, cell adhesion is important for guiding cell migration, differentiation, and the formation of complex structures. Processes like gastrulation and neural crest formation, where cells move and reorganize to establish the basic body plan, rely on precise cell adhesion events. The controlled ability of cells to adhere and detach allows for the sculpting of tissues and organs.
Immune Response
Cell adhesion also plays a role in the immune response. Immune cells, such as white blood cells, use adhesion molecules to navigate the bloodstream and extravasate (move out of blood vessels) to reach sites of infection or inflammation. This directed movement, often involving initial weak adhesion by selectins followed by stronger integrin-mediated binding, is important for the body’s defense mechanisms.
Wound Healing
Cell adhesion is important for wound healing and tissue repair. When tissue is damaged, cell adhesion molecules facilitate the migration of cells, such such as fibroblasts and epithelial cells, into the wound area. They contribute to wound closure, new tissue formation, and extracellular matrix remodeling, ensuring effective repair and regeneration.
When Cell Adhesion Goes Wrong
Dysfunctional cell adhesion can have consequences, contributing to the development and progression of various diseases. One recognized implication is in cancer metastasis. Altered expression or function of cell adhesion molecules allows cancer cells to detach from the primary tumor, migrate through the bloodstream or lymphatic system, and establish new tumors in distant parts of the body.
Inflammatory Diseases
Dysregulated cell adhesion also contributes to inflammatory diseases. In conditions like chronic inflammation, errors in immune cell adhesion and migration can lead to an exaggerated or prolonged inflammatory response, causing tissue damage. This is observed in various autoimmune disorders, where the immune system mistakenly attacks healthy tissues, partly due to aberrant cell-cell interactions and adhesion.
Genetic Disorders
Certain genetic disorders are linked to defects in specific adhesion molecules. For instance, some inherited skin blistering disorders result from mutations in genes coding for proteins involved in hemidesmosomes, leading to a weakened connection between skin layers. These examples show the link between proper cell adhesion and overall health.