Cell AdhesionEdit
Cell adhesion refers to the process by which cells attach to neighboring cells and to the surrounding extracellular matrix. This attachment is essential for organizing cells into tissues, shaping developing organisms, guiding cell movement, and maintaining the structural integrity of organs. Adhesion is mediated by a diverse set of cell surface proteins collectively known as cell adhesion molecules (CAMs). The strength and specificity of these interactions are finely tuned by cellular signaling, mechanical forces, and the extracellular environment, enabling both stable tissue architecture and dynamic remodeling as needed by growth, repair, and immune responses.
The study of cell adhesion sits at the intersection of biology, biomechanics, and materials science. It informs our understanding of development, cancer, wound healing, and chronic disease, while also guiding advances in regenerative medicine and biotechnology. In a more applied sense, therapies and biomaterials increasingly exploit adhesion mechanisms—whether to promote healing, inhibit metastasis, or create surfaces that encourage tissue integration.
Key mediators of adhesion
Cells employ several major families of CAMs to establish contacts and transduce signals across the cell membrane.
Cadherins
Cadherins are calcium-dependent CAMs that primarily mediate homophilic cell–cell adhesion, helping to hold epithelial and other tissues together. Classic examples include E-cadherin, which is crucial for epithelial sheet integrity, and N-cadherin, which plays roles in neural and cardiac tissues. Cadherins link to the actin cytoskeleton through intracellular catenins, forming adherens junctions that coordinate tissue architecture and respond to mechanical forces. Altered cadherin expression or function is a hallmark of many developmental processes and diseases, including cancer progression via epithelial-to-mesenchymal transition epithelial-mesenchymal transition.
Integrins
Integrins are heterodimeric receptors composed of α and β subunits that bind components of the extracellular matrix (ECM) such as fibronectin, collagen, and laminin. They enable cell–ECM adhesion and participate in bidirectional signaling: outside-in signals convey information about the ECM to the cell, while inside-out signals regulate integrin affinity and clustering. Integrin-mediated adhesions form focal adhesions and other complex structures that couple the cytoskeleton to the ECM, guiding cell migration, differentiation, and survival. Integrin signaling is a major conduit for mechanotransduction, the conversion of mechanical cues into biochemical responses.
Selectins
Selectins are a family of CAMs that mediate transient cell–cell interactions in the vasculature, especially during immune surveillance and inflammation. They enable rolling adhesion of leukocytes along the endothelium, a prerequisite for exiting the bloodstream and reaching sites of injury or infection. The selectin family includes L-, E-, and P-selectins, each with distinct expression patterns and roles in immune cell trafficking.
Immunoglobulin superfamily CAMs (Ig-CAMs)
The immunoglobulin superfamily encompasses a broad group of CAMs that mediate heterophilic and homophilic interactions. Notable members include ICAMs and VCAMs, which participate in leukocyte adhesion and transmigration, as well as neural and vascular adhesion molecules that contribute to tissue organization. Ig-CAMs interact with integrins and other receptors to coordinate immune responses, development, and vascular biology.
Mechanisms and signaling
Adhesion receptors are not passive anchors; they actively participate in signaling cascades that regulate cell fate, shape, and movement. Clustering of CAMs at adhesion sites recruits cytoskeletal adapters and kinases, shaping cytoskeletal organization and generating forces that cells sense and respond to. This mechanotransduction influences gene expression, differentiation, and adaptive remodeling of tissues. The balance between adhesive strength and contractile forces determines events such as collective cell migration, wound closure, and morphogenesis.
Roles in development and tissue organization
During development, precise adhesion dynamics guide tissue boundaries, organ formation, and polarization of cells within epithelia and other structures. Proper CAM function ensures orderly layering of tissues, compartmentalization, and fidelity of signaling pathways that rely on cell–cell or cell–matrix contacts. In mature organisms, adhesion systems contribute to tissue homeostasis, wound healing, and the maintenance of barrier functions across organs such as the skin, gut, and vasculature.
Pathology and disease
Disruptions or subversions of adhesion processes can contribute to disease. Loss of epithelial cadherin function, for example, is associated with increased invasiveness in cancers as cells detach from their neighbors and acquire migratory capabilities. Changes in integrin signaling can influence tumor progression, angiogenesis, and tissue remodeling in fibrosis. Adhesion molecules also participate in inflammatory responses and autoimmune phenomena, where inappropriate adhesion or trafficking of immune cells can exacerbate tissue damage.
Foreign or misregulated adhesion is a target for therapy in some contexts. For instance, strategies that block specific integrins or selectins have been explored to limit metastasis or dampen inflammatory responses, while biomaterials aim to present adhesion motifs that promote tissue integration and healing. In cancer therapy, agents that interfere with adhesion-related pathways can complement approaches targeting proliferation and survival.
Technologies and applications
Advances in our understanding of adhesion mechanisms have driven innovations in regenerative medicine and biomaterials. Engineered surfaces and scaffolds often incorporate adhesion ligands, such as RGD motifs, to promote cell attachment and guide tissue formation. Tissue engineering and regenerative strategies rely on controlled adhesion to build functional, vascularized tissues. In diagnostics and therapeutics, modulation of CAM interactions offers avenues to influence immune cell trafficking, tumor cell behavior, and wound repair. Notable examples include research into integrin inhibitors and strategies that mimic ECM components to steer cell fate and healing responses.