Understanding the principle biophysics concepts of pulmonary surfactant in health and disease

Abstract

Pulmonary surfactant (PS) is a lipid-protein complex essential to stabilise the delicate structure of mammalian alveoli along with successive compression-expansion respiratory cycles. To do so, surfactant reduces dramatically surface tension at the air-liquid interface, an activity that depends critically on a proper lipid composition and the presence of some specific surfactant proteins. Lack or dysfunction of this system is associated with severe respiratory pathologies, which are in some cases treated by supplementation with exogenous surfactant materials. The biophysical function and performance of PS, in health and disease, are directly influenced by its composition, structure and mechanical properties. This review summarises the main biophysics concepts behind the mechanisms that define surfactant function in a healthy lung and in pathological situations. It also revises some of the most useful biophysical techniques that provide information about surfactant-related processes. Finally, translational biophysics will be invoked to illustrate how biophysical studies may contribute to understand the role of surfactant in health and disease and to design better surfactant-based therapeutic approaches.

Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging

“…Impaired pulmonary surfactant activity in aged wild-type lungs is anticipated in telomerase-deficient mice We next set out to address the potential age-derived biophysical changes in lung surfactant activity in both Tert +/+ and G3 Tert −/− mice. To do so, we tested the biophysical properties of pulmonary surfactant isolated from bronchoalveolar lavages in a captive bubble surfactometer (Autilio and Pérez-Gil, 2019).…”

“…It is of particular interest that the majority of senescent cells were found to be AMs that have a crucial role in maintaining the correct surfactant homeostasis, preventing the accumulation of already used surfactant at the air-liquid interface with a limited biophysical performance (Autilio and Pérez-Gil, 2019). An impairment of surfactant activity has been already proposed as an early marker of fibrosis in a model of bleomycin-induced fibrosis in mice (Lopez-Rodriguez et al, 2016).…”

In Vitro Functional and Structural Characterization of A Synthetic Clinical Pulmonary Surfactant with Enhanced Resistance to Inhibition

“…To get deeper into this topic, we studied the in vitro inhibition of the three surfactants in the presence of serum. In fact, during lung inflammation and altered epithelial permeability, as it occurs in cases of ARDS, serum is leaked into the alveolar spaces and, among its several components that may perturb surfactant membranes, serum proteins may directly inactivate surfactant function, as a consequence of a direct competition for the air-liquid interface 7,24 . The low compressibility of serum proteins does not allow for the extreme reduction in surface tensions that are required to prevent alveolar collapse.…”

“…The low compressibility of serum proteins does not allow for the extreme reduction in surface tensions that are required to prevent alveolar collapse. Other inflammation-associated proteins like CRP 25,26 or secretory phospholipase A2 24,27 also contribute, altogether, to inhibit surfactant performance. In our in vitro model, CBS results confirm a similar performance of CHF in the absence or presence of serum, including the possible exclusion of POPG that would be associated with the characteristic plateau of the isotherm during dynamic cycles.…”

Severity of Coronavirus Disease 2019 (COVID-19): Does Surfactant Matter?

“…This lipid-protein complex is essential for the biophysical function of the lung. It stabilizes the delicate structure of the mammalian alveoli along with successive compression-expansion respiratory cycles by reducing surface tension at the air-liquid interface (Autilio and Pérez-Gil, 2019). In addition, this mixture of lipids and proteins constitute a first barrier to the access of pathogens to the rest of the organism via the large respiratory surface, preventing the dissemination of pathogens and modulating immune responses (Han and Mallampalli, 2015;Autilio and Pérez-Gil, 2019).…”