Possmayer Fred, Zuo Yi Y, Veldhuizen Ruud A W, Petersen Nils O
Department of Biochemistry, Western University, London, Ontario N6A 3K7, Canada.
Department of Obstetrics/Gynaecology, Western University, London, Ontario N6A 3K7, Canada.
Chem Rev. 2023 Dec 13;123(23):13209-13290. doi: 10.1021/acs.chemrev.3c00146. Epub 2023 Oct 20.
Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.
肺表面活性物质是健康个体肺功能的关键组成部分。它部分通过降低肺泡表面张力来发挥作用,从而使呼吸轻松自如。目前普遍的观点认为,在呼气过程中,不饱和磷脂通过压缩驱动的挤出作用降低表面张力,形成富含饱和磷脂的薄膜,使表面张力接近零。对过去和近期文献的全面回顾表明,压缩驱动的挤出机制可能是错误的。在此,我们提出富含饱和脂质的表面活性物质薄膜在出生后不久通过吸附驱动的分选过程形成,并且其组成在正常呼吸过程中不会改变。我们提供了生物物理证据,证明在高表面活性物质浓度下,由含有疏水表面活性蛋白的吸附结构促进,富含饱和脂质的薄膜会迅速形成。我们研究了支持和反对压缩驱动挤出机制的生物物理证据,并提出了一种新的表面活性物质功能模型。该模型针对新生儿和成人肺部现有的生理和病理生理证据进行了测试,从而引发了生物物理研究的思路,要确立这种关于表面活性物质提供的强大薄膜功能的新观点的生理相关性,就应该解决这些思路。