The air-liquid interface (ALI) describes a boundary where air meets a liquid surface within a biological system. This interface is fundamental to the functioning of many living organisms, particularly in processes involving interaction with the external environment. Its presence allows for specialized biological activities not possible in fully submerged or dry environments.
The Concept of the Air-Liquid Interface
The air-liquid interface naturally occurs in several areas of the human body, serving distinct physiological purposes. A prominent example is the lining of the lungs, specifically the airway epithelium, where air meets a thin fluid layer. This interface facilitates gas exchange, allowing oxygen to enter the bloodstream and carbon dioxide to exit. Similar interfaces exist on the skin, where the outermost layer interacts with air while supported by underlying tissue fluids. The intestinal barrier also presents a form of air-liquid interface, though it involves digested food contents rather than ambient air.
These interfaces are structured to enable specific biological functions. In the lungs, the mucociliary escalator, a system of mucus-producing cells and ciliated cells, works at the air-liquid interface to trap and remove inhaled particles and pathogens, protecting the delicate lung tissue. The fluid layer also contains protective mediators like antimicrobial peptides. In the gut, similar barrier functions prevent harmful substances from entering the bloodstream while allowing nutrient absorption. The unique environment at these interfaces, characterized by differing concentrations of gases and dissolved substances, drives processes such as ion transport and fluid secretion.
Mimicking Biology with Air-Liquid Interface Models
Scientists create artificial air-liquid interface (ALI) models in laboratories to replicate physiological conditions found in the body. Traditional submerged cell cultures, where cells are completely covered in liquid, often fail to fully mimic the complex environment of tissues exposed to air. ALI models overcome this by providing cells with air exposure on one side and nutrient supply from a liquid on the other.
The methodology for creating ALI models involves culturing cells, often primary epithelial cells from human airways, on a porous membrane. Initially, cells are grown submerged in culture medium until they form a confluent layer. The medium is then removed from the upper, or apical, compartment, exposing the cells to air while the basal side remains in contact with nutrient-rich liquid media supplied through the porous membrane. This “air-lift” process allows cells to differentiate and develop specialized structures and functions, such as cilia and mucus production, characteristic of their natural environment.
These models offer advantages over traditional cultures. They promote improved cell differentiation, leading to a more accurate representation of tissue architecture and function. For example, airway epithelial cells cultured at the ALI can develop into a pseudostratified epithelium with ciliated and mucus-secreting goblet cells, closely resembling the in vivo airway. This enhanced physiological relevance makes ALI models useful for studying biological processes and disease mechanisms in a controlled laboratory setting, reducing reliance on animal models.
Key Applications in Scientific Research
Air-liquid interface models have widespread application in scientific research, particularly where understanding tissue-air interaction is important. They are widely used to study respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. By culturing airway epithelial cells from patients, researchers can investigate disease mechanisms and test potential treatments in a physiologically relevant setting. For instance, ALI models have been used to study the defective ion and water transport in cystic fibrosis that leads to thick mucus.
ALI models are also used to study viral infections that target the respiratory tract, including influenza and coronaviruses like SARS-CoV-2. These models allow scientists to observe the entire infection process, from viral entry to replication and the host immune response, in a controlled environment. This capability has advanced the understanding of how these viruses infect human airway cells.
ALI models are also used for drug development, especially for inhaled medications, as they allow direct application of aerosolized drugs to the cell surface, mimicking real-world delivery. They are also used in toxicology testing to assess the effects of airborne pollutants, nanoparticles, and aerosols on respiratory cells. Beyond the respiratory system, ALI models are being explored for understanding barrier functions in other tissues, such as the skin for wound healing and dermal remodeling, and the gut.