# Three-dimensional Confocal Microscopy Visualization and AFM-IR Chemical Mapping of Lung Surfactant Monolayer Collapse Morphologies

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2024 · $45,223

## Abstract

ABSTRACT
Neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS) afflict upwards
of 250,000 Americans every year. NRDS affects premature infants due to their underdeveloped lung’s inability
to produce sufficient functional lung surfactant. Animal replacement surfactant treatment options exist for NRDS,
although concerns over bio-variability, interspecies disease transmittance, and religious questions over porcine
versus bovine derived surfactants remain. ARDS was seen in ~75% of all admitted COVID-19 ICU patients and
is currently untreatable leading to a mortality rate of ~40%. ARDS is initiated by lung trauma or disease that
leads to inflammation, causing an uncharacteristic increase of the surface tension within the lungs, leading to
atelectasis. A deeper understanding of the fundamental structure and limiting behavior of lung surfactant
monolayers may be the avenue to suggest new synthetic replacement surfactant treatments that could mitigate
the biological concerns in NRDS as well as develop treatment options for patients with ARDS. My group has
previously identified that the “collapse” of a monolayer determines the lower surface tension limit during the
alveolar area compression accompanying exhalation. The physical and chemical factors that govern collapse
may be altered in patients who develop dysfunctional, high surface tension lung surfactant during ARDS.
Monolayers of healthy lung surfactant phase separate into domains of a semi-crystalline ordered phase and a
disordered liquid phase of varied composition. We hypothesize that this phase separation dictates many of
the dynamic and rheological properties of the monolayer that influence collapse. However, there is little
direct information on the composition of the different domains in multicomponent lung surfactants. I will address
monolayer collapse and phase separation in the following two aims. In Aim 1, I will visualize monolayer collapse
structures using the 3-D serial sectioning capabilities of the confocal fluorescence microscope to determine how
monolayer domains alter collapse behavior and the minimum surface tension. I have also recently found that
collapse behavior changes on curved, alveolar-size interfaces compared to the flat surfaces in a Langmuir
trough, and I will use confocal imaging to determine the relationship between collapse morphology and interfacial
curvature. Aim 2 is to pioneer infrared-coupled atomic force microscopy (AFM-IR) methods to map the lateral
distribution of the chemical species and their local ordering in multicomponent lung surfactant monolayers. I will
use AFM-IR to examine the hypothesis that cholesterol concentrates at domain boundaries to lower the line
tension while palmitic acid and hexadecanol promote crystallization of dipalmitoylphosphatidylcholine, increasing
the fraction of solid phase in the monolayer. Successful completion of this project will provide a detailed
description of the two-dimensional che...

## Key facts

- **NIH application ID:** 10996085
- **Project number:** 5F31HL170778-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Zachary D McAllister
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,223
- **Award type:** 5
- **Project period:** 2023-09-15 → 2026-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996085

## Citation

> US National Institutes of Health, RePORTER application 10996085, Three-dimensional Confocal Microscopy Visualization and AFM-IR Chemical Mapping of Lung Surfactant Monolayer Collapse Morphologies (5F31HL170778-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10996085. Licensed CC0.

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