Discuss briefly the general principles of cellular adhesion. Give a note on identification and characterization of adhesion receptors.

General Principles of Cellular Adhesion

Cellular adhesion isn't a random process; it's governed by several key principles:

• Specificity: Adhesion is highly specific, mediated by interactions between complementary adhesion molecules on cell surfaces. This ensures that cells adhere to the correct partners.
• Valency: The strength of adhesion depends on the number of interactions between adhesion molecules. Multiple, weak interactions can collectively provide strong adhesion.
• Regulation: Adhesion is dynamically regulated by various factors, including signaling pathways, mechanical forces, and the cellular environment. This allows cells to alter their adhesive properties in response to changing conditions.
• Energy Minimization: Cells tend to maximize contact with their surroundings to minimize surface energy, driving adhesive interactions.
• Distance Dependence: Most adhesion molecules require close proximity between cells or between cells and the ECM to facilitate binding.

Identification and Characterization of Adhesion Receptors

Adhesion receptors are transmembrane proteins that mediate cell-cell and cell-matrix interactions. They can be broadly categorized into four major families:

1. Cadherins

Cadherins are calcium-dependent adhesion molecules primarily involved in cell-cell adhesion. They mediate homophilic interactions, meaning they bind to other cadherins of the same type. Different types of cadherins (e.g., E-cadherin, N-cadherin, P-cadherin) are expressed in different tissues and contribute to tissue-specific adhesion. Loss of E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT) and is frequently observed in cancer metastasis.

Characterization: Cadherins are identified by their calcium-binding properties, extracellular cadherin domains, and association with intracellular catenins (α, β, and p120). Antibodies against cadherins and their associated proteins are commonly used for identification. Western blotting and immunofluorescence microscopy are standard characterization techniques.

2. Immunoglobulin Superfamily (IgSF)

The IgSF comprises a diverse group of adhesion molecules characterized by the presence of immunoglobulin-like domains. They mediate both homophilic and heterophilic interactions. Examples include NCAM (Neural Cell Adhesion Molecule), ICAM (Intercellular Adhesion Molecule), and VCAM (Vascular Cell Adhesion Molecule). These molecules play crucial roles in immune responses, neuronal development, and inflammation.

Characterization: IgSF members are identified by their immunoglobulin-like domains, which can be detected using antibodies. Flow cytometry and ELISA are used to quantify their expression levels. Binding assays are used to determine their interaction partners.

3. Integrins

Integrins are heterodimeric transmembrane receptors that mediate cell-matrix and cell-cell adhesion. They bind to ECM components like fibronectin, collagen, and laminin. Integrins also play a role in signal transduction, influencing cell survival, proliferation, and differentiation. They are crucial for processes like wound healing and angiogenesis.

Characterization: Integrins are identified by their α and β subunit composition. Antibodies specific to different integrin subunits are used for identification. Cell adhesion assays using ECM proteins are used to assess their binding affinity. Integrin activation can be monitored using conformational changes detected by specific antibodies.

4. Selectins

Selectins are carbohydrate-binding adhesion molecules that mediate transient interactions between cells and the endothelium. They are involved in leukocyte recruitment to sites of inflammation. There are three types of selectins: E-selectin, P-selectin, and L-selectin. They bind to carbohydrate ligands (sialyl Lewis x) on leukocytes.

Characterization: Selectins are identified by their lectin-like domains. Binding assays using labeled carbohydrate ligands are used to assess their binding specificity. Flow cytometry is used to detect their expression on endothelial cells and leukocytes.

Adhesion Receptor Family	Interaction Type	Key Functions	Examples
Cadherins	Homophilic (Ca2+-dependent)	Cell-cell adhesion, tissue formation	E-cadherin, N-cadherin
IgSF	Homophilic/Heterophilic	Immune responses, neuronal development	NCAM, ICAM, VCAM
Integrins	Heterophilic (ECM binding)	Cell-matrix adhesion, signal transduction	α5β1, αvβ3
Selectins	Heterophilic (Carbohydrate binding)	Leukocyte recruitment, inflammation	E-selectin, P-selectin