Discovering structure–property–function relationships in pulmonary membranes and their role in lung pathophysiology

Porras-Gomez, Marilyn

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https://hdl.handle.net/2142/120528 Copy

Description

Title

Discovering structure–property–function relationships in pulmonary membranes and their role in lung pathophysiology

Author(s)

Porras-Gomez, Marilyn

Issue Date

2023-04-23

Director of Research (if dissertation) or Advisor (if thesis)

Leal, Cecilia

Doctoral Committee Chair(s)

Leal, Cecilia

Committee Member(s)

• Espinosa-Marzal, Rosa M
• Cao, Qing
• Wang, Hua

Department of Study

Materials Science & Engineerng

Discipline

Materials Science & Engr

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Pulmonary membranes
• biophysics, structure-property-function
• lung pathophysiology
• biomaterials

Abstract

The mammalian lung evolved to enable highly efficient gas exchange in the alveoli while mechanically adapting to constant expansion and contraction during the breathing cycle. These remarkable properties are mediated by the alveolar lining composed of lipids and proteins often referred to as lung surfactant. The most well-established function of the surfactant monolayer is to reach and sustain very low surface tensions. Furthermore, the lung surfactant connects to the pulmonary membranes, a lipoprotein complex and dynamic system inhabiting the alveolar hypophase. Altogether, these membranes regulate lung mechanics, facilitate gas exchange, and provide innate immunity, all primary functions in respiratory physiology. Consequently, alterations in pulmonary membrane homeostasis have been linked to lung pathology in general, but integrative understanding of the potential contribution of pulmonary membrane alterations to lung disease mechanisms remains elusive. This dissertation focuses on identifying structure–property function relationships to bridge the gap between the biophysical properties and behavior of pulmonary membranes, and their manifestation across pathological conditions in the lungs, such as pneumonia. My research explores pulmonary membrane functionality by interrogating their composition, structure, and mechanics beyond surface tension, and correlating them with known features of lung pathology. This is attained by evaluating lipid-based membrane models, bovine lung extracts, dolphin native pulmonary membranes, and lung tissue from a materials science perspective. A combination of optical and atomic force microscopy with a surface force apparatus shows that pneumonia conditions dramatically decrease the energy barrier for membrane hemifusion, leading to the quick formation of intermembrane contacts that disrupt the oxygen permeation, which is measured using a graphene-based sensor. Such gas imbalance results in hyperoxia, likely potentiating both bacterial growth and inflammatory responses. The membrane contacts also lead to a decrease in pulmonary membrane and tissue elasticity, which is probably associated with difficulty breathing. Additionally, this research explores the collective response of lung multilayered membranes to compression resulting from membrane undulations and lipid molecule tilting using X-ray scattering. Finally, the evaluation of dolphin-native lung membranes naturally suffering from respiratory illnesses –performed through lipidomics, X-ray scattering, and microscopy– links the severity of lung pathology with membrane lateral domain reorganization, and changes in structure and mechanics. Altogether, these factors resulting from lung pathogenesis collectively impair pulmonary membrane functionality, likely contributing to the etiology and outcome of lung diseases. This dissertation provides implications that will serve as a basis for developing better therapeutics that target specific mechanisms of lung diseases such as pneumonia at the membrane level. Finally, this research contributes to filling the gap between our knowledge of mammal lung pathophysiology and the biophysical properties of pulmonary membranes.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Marilyn Porras-Gomez

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