Research Progress on Air-liquid Interface Activity and Function in

Respiratory Tract and Digestive Tract

Xinghui Wu

1,2 a

, Mingjie Xia

1,2

, Shufang Cao

1,2

, Wenqi Cai

1,2

, Li Li

1,2

and Lina Yang

1,2,*

College of Food Science and Engineering, Bohai University, 121013, Jinzhou, Liaoning, China

Grain and Cereal Food Bio-efficient Transformation Engineering Research Center of Liaoning Province, 121013,

Jinzhou, Liaoning, China

*Corresponding author

Keywords: Air-Liquid Interface, Interfacial Activity, Functional Food.

Abstract: Air-liquid interface activity is closely related to the health of the body. The change of interfacial activity

affects the normal physiological functions, such as the internal environment, microecological balance and

nutrient absorption and utilization of the body. In order to provide a new idea for the evaluation and pre-

treatment of respiratory and digestive diseases, and provide theoretical support for the development of

functional food. The formation mechanism of gas-liquid interface is introduced, the relationship between gas-

liquid interface activity and respiratory tract and digestive tract is combed, and the factors affecting the

interface activity are summarized.

1 INTRODUCTION

The air-liquid exchange interface in the body has a

significant impact on the normal physiological

function of organs. In the unhealthy state, the activity

of the air-liquid interface will change accordingly.

The occurrence of respiratory diseases such as

asthma, bronchitis, chronic obstructive pulmonary

disease, oral, gastric and inflammatory bowel

diseases goes hand in hand with the change of air-

liquid interface activity. Asthma and other airway

inflammatory diseases are accompanied by a

significant increase in airway mucus viscoelasticity

(Johnson 2011). In the lungs of patients with

respiratory distress syndrome, protein rich pulmonary

edema can inhibit or destroy the habitual function of

surfactants, resulting in increased surface tension of

pulmonary fluid (Luo et al. 2017). Inflammatory

bowel disease is accompanied by lipid peroxidation

and decreased antioxidant capacity, resulting in an

imbalance between oxidation and antioxidant,

increasing surface pressure. The increase of surface

pressure causes damage to small intestinal mucosa

(Xie ＆ Wan 2020).

https://orcid.org/0000-0001-8481-667X

Although more and more studies have found that the

air-liquid interface plays a key role in the occurrence

and prevention of diseases, the causal relationship

between the activity of the air-liquid interface and the

occurrence of diseases and the related molecular

mechanism is not clear. This review expounds and

summarizes the formation of air-liquid interface, the

application of air-liquid interface activity in the health

evaluation of respiratory system and digestive

system, and the factors affecting interface activity. In

order to provide a unique perspective for the

prevention and treatment of related diseases, and

provide a theoretical reference for the design and

production of functional foods for the treatment and

prevention of related diseases.

2 FORMATION OF GAS-LIQUID

INTERFACE

The surface of the oral cavity, airway, stomach,

intestine and other organs of the organism is covered

with a thickness of 2-10 μM mucus layer (Puchelle et

al. 1987), which is the first line of defense of human

immune system (Bajka et al. 2015). It plays a role in

124

Wu, X., Xia, M., Cao, S., Cai, W., Li, L. and Yang, L.

Research Progress on Air-liquid Interface Activity and Function in Respiratory Tract and Digestive Tract.

DOI: 10.5220/0011233200003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 124-130

ISBN: 978-989-758-596-8

resisting the invasion of bacteria, viruses and harmful

compounds. Mucus is a gelatinous polymer

composed of glycosylated mucin, containing 90%-

95% of water, 1%-2% lipids and electrolytes (Paola

2020, Widdicombe ＆ Wine 2015). Therefore, mucus

has complex rheological properties, such as shear

thinning, viscoelasticity, adhesion (Puchelle et al.

1987). The exertion of various physiological

functions of the body largely depends on the

appropriate rheological properties of mucus. In the

respiratory system, the protective and scavenging

function of airway mucus is dependent on the

appropriate rheological properties of mucus,

otherwise airway mucus may become a factor of

airway obstruction. For example, the airway of

asthmatic patients will over secrete mucus with high

viscosity, resulting in poor fluidity of mucus and

difficult to discharge from the airway. In severe cases,

airway mucus embolism will be formed in the airway

(Johnson 2011), resulting in atelectasis, asphyxia,

respiratory failure and even sudden death (Luo et al.

2017). In the digestive system, human digestive tract

mucus plays an important role in the digestion and

transportation of food in the gastrointestinal tract and

the lubrication and protection of gastrointestinal

mucosal surface (Zhou et al. 2004). Moreover,

intestinal fluid rheology is also closely related to the

colonization, distribution and growth of intestinal

flora, and then affects the absorption effect of

nutrients and drugs (Boegh et al. 2014).

There is a surface layer of the contact between the

mucus layer and the external atmospheric

environment, referred to as the air-liquid interface.

The surface response of air-liquid interface to

dynamic conditions is closely linked to the stability

and health of various tissues and organs. In the

development of natural science and light industry, the

application of air-liquid interface activity has been

widespread. For example, the production principle of

Yuba is to denature the protein in soybean milk by

heating. The hydrophobic groups inside the protein

are exposed, while the hydrophilic groups outside the

protein are transferred to the inside of the molecule.

The protein is concentrated, collided and condense,

precipitate, and gradually grow into a film. Then, the

sugar is adsorbed on the protein by van der Waals

force or hydrogen bond to gradually form a certain

toughness of Yuba (Chen 2010). However, there is

little understanding of how the air-liquid interface in

a human body affects the normal physiological

function of various tissues and organs. The main

reason is that the structure of the human body is much

more complex than that of other organisms. And it

belongs to soft matter from the perspective of

materials, which are essentially different from

inorganic materials (Jin 2014). Therefore, it’s great

significance for understanding the mechanism of

physiological activities and disease occurrence and

development to study the air-liquid interface with

special functions in the human body at the micro

scale.

3 ACTIVITY AND FUNCTION OF

AIR-LIQUID INTERFACE IN

RESPIRATORY TRACT

3.1 Nose

The surface of nasal mucosa is the subject with a

mucus blanket with a thickness of 5-10 μm. It can

adsorb about 80% of the particles in the gas, and the

mass of these particles is greater than 12.5 μg (Zhang

et al. 2006). Mucociliary blanket and ciliated

epithelial layer below it constitute nasal mucociliary

transmission system, which is an important

mechanical defense system of human body. Guo

Yongqing (Guo et al. 2004) tried to construct a

Construction of ciliary differentiation model of

cultured human nasal epithelial by using air-liquid

interface culture technology, and quantitatively

analyzed the degree of ciliary differentiation. The

research provide an advanced research means for

exploring the physiological and pathological

characteristics of respiratory epithelial cells. Zhao

Yanyan (Zhao et al. 2020) infected human nasal

epithelial cells cultured at the air-liquid interface with

Staphylococcus aureus standard strains and clinical

isolates of chronic rhinosinusitis, and analyzed the

effects of Staphylococcus aureus infection on the

tight junction and cell viability of nasal epithelial

cells.

3.2 Hung

The human airway is covered by mucus layer. The

changes of rheological properties such as mucus

viscosity and surface tension affect the physiological

functions such as airway stability, lung defense

barrier and mucociliary clearance. Long Yun (Long

et al. 2006) and others think that the collapse of

airway compliance largely depends on the pressure

load of surface tension on airway wall. Due to the

compression of the airway, the increase of the

curvature of the air-liquid interface will increase the

surface tension, resulting in the increase of the load

on the airway wall, and finally affect the compliance

Research Progress on Air-liquid Interface Activity and Function in Respiratory Tract and Digestive Tract

125

of the airway wall. Pulmonary surfactant (PS) is a

lipid complex protein mixture. It covers the alveolar

surface and makes the respiratory function normal by

reducing the surface tension at the air-liquid interface

(Wang＆Hu 2020). At the same time, it also has the

functions of stabilizing the airway and protecting

against the pulmonary edema (Liu et al. 2020). Ann

M. czyzewski (Czyzewski et al. 2018) et al. used

biomimetic lipid mixture to simulate the

physiological activity of pulmonary surfactant

proteins B and C at the air-liquid interface. The study

provides a strong theoretical basis for the new

medical research that natural surfactants can

effectively treat acute lung injury. Ji Xiaoli (Ji et al.

2021) constructed a primary culture model of mouse

tracheal epithelial cells by air-liquid interface culture.

It was applied to the evaluation of the inhalation

toxicological in vitro.

4 ACTIVITY AND FUNCTION OF

AIR-LIQUID INTERFACE IN

DIGESTIVE TRACT

4.1 Oral Cavity

Human saliva is mainly produced in the oral cavity by

the parotid gland, submersible gland and the

sublingual gland. It is a major biological liquid to

maintain oral health. Saliva not only serves as a

barrier to pathogens, but also promotes food intake. It

also provides a medium for dissolved and suspended

food substances to stimulate the taste. As the core

component of salivary membrane covering teeth,

mucin plays a role in helping lubricate, protect and

heal oral mucosa (Liu 2018). Rossetti (Rossetti et al.

2013, Rossetti et al. 2013) examined the effect of the

interaction between proteins of human oral saliva and

different polyphenols on the expansion

characteristics of air-liquid interface during oral

digestion. Firstly, the complexity of kinetics and

interfacial expansion rheology of salivary membrane

was investigated. The results showed that small

molecular weight protein components adsorbed on

the interface and produced solute like surfactant

reaction, but the adsorption of higher molecular

weight proteins makes the interface more and more

insoluble.

4.2 Stomach

There are many kinds of internal and external

secretory cells in gastric mucosa, such as principal

cells, parietal cells and G cells. Its synthetic and

released gastric juice and various gastrointestinal

hormones are widely involved in digestion and

absorption (Liu et al. 2020). Mucosa can protect the

stomach from gastric acid erosion. Once damaged,

the stomach will be invaded by gastric acid and

bacteria for a long time. In severe cases, it will be

expected to result in gastric ulcer, gastric perforation

and other diseases (Jin 2014). Helicobacter pylori

infection will destroy the structure and function of

gastric mucosal epithelium. Jin Lin (Jin 2014)

explored the mechanism of Helicobacter pylori

infection of gastric mucosal epithelium by

establishing H. pylori gastric mucosal epithelial air-

liquid interface. The study provides a theoretical basis

for the prevention and treatment of gastrointestinal

diseases caused by infection.

4.3 Intestine

In the intestine, the small intestine is the main port for

nutrient absorption. The lumen surface is composed

of intestinal epithelial cells and covered by a mucus

layer, which is a barrier against harsh digestive

environment (Huang 2021, Ou et al. 2021). Many

microbiota are colonized on the surface of intestinal

mucosa, which coexist with the human body and

maintains the normal physiological function of the

host. Once the flora structure is changed, the

proportion of bacteria is unbalanced, and the

metabolism will be disorder. It may lead to the

occurrence of various diseases such as diabetes

mellitus (Yao 2020). Studies have shown that

changes in duodenal fluid rheology usually affect the

colonization, distribution and growth of intestinal

flora, and then affect the absorption effect of nutrients

and drugs (Morrison ＆ Preston 2016). Johansson

(Johansson et al. 2015) et al. further found that the

number of goblet cells in the intestinal mucus of green

fluorescent mice was depressed, and the intestinal

mucus was anchored on the goblet cells and could not

be sucked out through the experiment. Compared

with conventional mice, green fluorescent mice have

poor intestinal mucus rheology and reduced air-liquid

interface activity. It makes intestinal flora colonize

difficultly, and then affecting the distribution and

growth of intestinal flora. TARGO (Tamargo et al.

2018) also show that the increase of colonic mucus

viscosity is conducive to the reproduction of

anaerobic bacteria, and the reproduction of the

intestinal flora will also increase the viscosity of the

culture system. The changes in the composition of

intestinal flora also reduce the thickness of the

intestinal mucus layer and increase mucus

ICHIH 2022 - International Conference on Health Big Data and Intelligent Healthcare

126

permeability (Wells et al. 2017). Some intestinal

probiotics have been proved to regulate intestinal

epithelial function by promoting the formation of

mucosal layer, secreting antibacterial factors,

promoting the secretion of secretory immunoglobulin

A and competitive adhesion with intestinal epithelial

cells (Liu et al. 2020), and reduce surface tension and

increase expansion modulus to maintain intestinal

barrier homeostasis and promote health.

Figure 1: Model of soy hull polysaccharides-protein in

simulated intestinal fluid (Huang 2020).

5 IMPACT FACTORS OF THE

ACTIVITY OF AIR-LIQUID

INTERFACE

5.1 Effect of Surfactant on

Interfacial Activity

Surfactant plays a decisive role in regulating the

viscosity of mucus and the rheological properties of

air-liquid interface. As shown in Figure 2, natural PS

provides surface activity of alveoli during respiration.

During inhalation, PS forms a surface active

membrane which adsorbs to the air-liquid interface to

cover the alveolar area. When exhaling, PS forms a

compressible multilayer structure. The surfactant film

is filled with PS that greatly reduces the alveolar

surface tension. When the alveolar dilation is caused

by re inhalation, the surfactant membrane expands

again. And the phospholipids at the air-liquid

interface redistribute laterally to cover the alveolar

area.

Figure 2: Schematic diagram of alveolar structure and

function (Dong et al. 2016).

Studies have shown that there is a substance

similar to PS in the eustachian tube, mainly composed

of phosphatidylcholine and protein. It can reduce the

surface tension of the ciliated mucus blanket on the

surface of the eustachian tube, and prevent the

adhesion of the tube wall and contribute to the

discharge of secretions. The reduction of surfactant is

not conducive to the opening of the eustachian tube

and the discharge of secretions (Zhu et al. 2013).

Fornadley (Dong et al. 2016) et al. found that by

injecting exogenous surfactant, the open pressure of

eustachian tube in gerbils with secretory otitis media

model decreased significantly and closed to the

normal value.

Due to the electrostatic attraction of opposite

charges, intestinal mucin can combine with some

lipids or polysaccharides to form surfactant. It can

change the activity of air-liquid interface. Luo

Xinyou (Luo et al. 2015) et al. treated sinusitis of

children with a composite surfactant composed of

soybean based grain extract and cationic surfactant

(chitosan quaternary ammonium salt). Through the

inhibitory effect of Chitosan on the biological

interface of Streptococcus mutants and the reduction

of toxicity and enhancement of bactericidal effect of

grain extract, the nasal ventilation and sinus drainage

are improved. Guri (Guri et al. 2015) et al. used

epithelial mucus extracted from human colon

adenocarcinoma cell HT29-MTX to explore the

interaction between tea polyphenols and milk protein

and intestinal mucus at the air-liquid interface. It is

found that the main component of tea polyphenols

(epigallocatechin-3-gallate) can bind to milk protein.

The formed complex reduces the interfacial surface

tension and increases the expansion modulus. It

indicate that nutrient molecules are more likely to

interact with intestinal mucus before they are

effectively transported and absorbed by intestinal

cells. The research of Huang Jinghang (Huang et al.

2020) shows that soybean hull polysaccharide may

form a similar polysaccharide mucin complex in the

intestinal digestion in the delivery system. Therefore,

in the process of interfacial adsorption, the interfacial

tension decreases and the interfacial expansion

modulus increases are conducive to the release and

absorption of nutrients. The study provides

theoretical support for the development of beneficial

functional foods of soy hull polysaccharide.

5.2 Effect of pH on Interfacial

Activity

A large number of experiments have proved that the

change of pH value will affect the activity of air-

liquid interface. By studying the film-forming law of

protein at the air-liquid interface, Hua Jian (Hua

Research Progress on Air-liquid Interface Activity and Function in Respiratory Tract and Digestive Tract

127

2003) found that the surface pressure will gradually

increase with the increase of pH value. And at

isoelectric point nearly, the both of the interface

activity and the ability to reduce surface tension are

also inferior, and the surface pressure is small. This

may be because the change of pH of the system will

lead to the change of charge, which will affect its

stability. Dong Lei (Dong et al. 2014) et al. found that

the change of charge density can inhibit the formation

of a tight adsorption layer at the air-liquid interface of

protein molecules and the increase of surface pressure

and expansion modulus. In addition, the change of pH

value of mucus will also affect the viscosity of mucus,

and then change the activity of air-liquid interface.

For example, some people believe that Helicobacter

pylori will not only increase the pH value of mucus,

but also reduce the viscoelasticity of mucus and

increase the mobility of mucus. It also can reduce the

activity of the air-liquid interface.

5.3 Effect of Ions on Interfacial

Activity

Ionic strength affects the adsorption kinetics of

particles at the air-liquid interface, and then affects

the interfacial activity. Wang Mei (Wang et al. 2020)

et al. analyzed the change of air-liquid interface

pressure under the strength of Na

and Ca

at pH 7.

They found that the greater the ionic strength, the

faster the surface pressure rises. This may be because

ions make the protein molecular structure more loose

and it is easier to adsorb to the air-liquid interface,

leading to the interfacial tension and increasing the

surface pressure. Moreover, the increase of ionic

strength will also enhance the flexibility of protein.

The hydrophobic groups of protein molecules are

more likely to be exposed to the air-liquid interface,

it can reduces the tension of the air-liquid interface

and accelerates the rate of expansion and

rearrangement. Zhang Xuan (Zhang et al. 2020) et al.

found that the surface tension equilibrium value

decreased with the increase of Ca

and Na

content.

It is mainly caused by the increase of adsorption

capacity of nanoparticles at the air-liquid interface. At

the air-liquid interface, the electrostatic repulsion

between particles is inversely proportional to the salt

content. Meanwhile, the negative repulsion between

particles and air-liquid interface will also decrease

with the increase of salt content, resulting in the

increase of particle adsorption density at the interface.

In addition, studies have shown that the contact angle

of particles will increase with the increase of ion

content (Wang et al. 2021), it makes the surface

tension decrease more obviously.

5.4 Effect of Antioxidants on

Interfacial Activity

At present, it has been found that a variety of

experimental intestinal mucosal injury and intestinal

diseases are related to the participation of aerobic free

radicals (Qian, et al. 2017). Lipid peroxidation and

the decrease of antioxidant capacity lead to the

imbalance between oxidation and antioxidant, the

increase of surface pressure and the damage of small

intestinal mucosa. Antioxidants can protect the

function of intestinal mucosal barrier by increasing

the activity of intestinal antioxidant enzymes,

scavenging oxygen free radicals, improving the state

of oxidative stress, improving tissue antioxidant

capacity and changing the activity of air-liquid

interface.

6 CONCLUSIONS

In recent years, with the development of science and

technology, air-liquid interfacial activity has long

been not only used to explain natural science and

applied in food industry, industry, manufacturing and

other production and processing. In terms of body

health evaluation, the air-liquid interface also plays

an important role. Although there are a few reports on

the formation of air-liquid interface, the function of

air-liquid interface activity in digestive tract and

respiratory tract and the factors affecting interface

activity, there are still many outstanding problems.

For example, the mechanism of air-liquid interface

activity regulating body health and the influence

mechanism of surfactant on interface activity are not

clear. However, based on the available information of

air-liquid interface activity, it can be determined that

air-liquid interface activity affects physiological

functions such as environmental stability of tissues

and organs, microecological balance and nutrient

absorption and utilization. It is hoped that with the

gradual deepening of people's research, the air-liquid

interface activity will provide unlimited possibilities

for the treatment of related diseases. And the idea that

the activity of air-liquid interface in vivo can be

adjusted by oral administration of exogenous

surfactants can be realized as soon as possible. At the

same time, the study of air-liquid interface also

provides multi angle demonstration for the functional

food to be developed.

ICHIH 2022 - International Conference on Health Big Data and Intelligent Healthcare

128

ACKNOWLEDGEMENTS

This study was supported by National Natural

Science Foundation of China (Grant No. 31901680).

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