# Multiscale Biochemical/Biophysical Integration of Pulmonary Mucus Transport

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $646,802

## Abstract

The pathogenesis of the chronic bronchitis component of pulmonary diseases, defined by chronic cough and
sputum production, is not well understood. Despite the bronchitic features of CF, PCD, COPD, and asthma,
there has been a general inability to relate changes in mucus properties to disease pathogenesis. The absence
of an adequate formulation to describe mucus transport and health, and predict the failure of mucus transport
in disease, has limited our knowledge in this area. A novel topographical description of airway mucus the (“gel
on brush” model), coupled with a novel application of polymer physics concepts, has been applied to the local
biophysical processes that govern mucus flow in health and the failure to flow in disease. However, a full
description of the mucus clearance system and health and disease requires a more global/multi-scaled
description of mucin/mucus biology in the lung. At one length scale, we need to understand the integration of
mucin secretion and flow in different regions of the lung and how secretions from glands and superficial
epithelia are admixed in proximal airways to maintain basal flow and respond to irritants by cough. At another
length scale, we need to know why mucins require their gigantic size and how these very large molecules are
released and integrated into the local airway surface liquid environment. We have selected four key gaps in our
understanding of the mucociliary system for investigation. These gaps constitute our four specific aims.
Specific Aim 1 How is mucin secretion organized intraregionally in superficial epithelia and proximally with
submucosal gland secretion? This aim will test the hypothesis that a new paradigm for mucin secretion in the
lung is required, focusing on the role of basal MUC5B secretion in the distal airways (rather than proximal
airway glands) in the lung. Specific Aim 2: Are there functional differences in mucus secreted by superficial
epithelia vs glands? This aim will test the hypothesis that the mucins secreted by superficial epithelial
constitute a “reversible” gel that dissolves into the local ASL environment whereas mucin secreted from glands
constitute a “permanent” gel configured for plug-like flow/coughability. Specific Aim 3: How are mucins
released from granules onto the airway surface? This aim will attempt to distinguish between the hypotheses
that are mucins are released in response to an electrostatic Na+ for Ca2+ entropic exchange mechanism vs a
HCO-3/pH +/- protease dependent mechanism. Specific Aim 4: Why are mucins organized into gigantic
(>100MD) higher-order multimers? The hypotheses tested are that gigantic molecules are required to generate
mucus gels with biophysical properties commensurate with transport in dilute solutions and that such large
molecules impose unique cell biologic packaging constraints on the cell. Importantly, resolution of the
questions/hypotheses generated by this analysis of “gaps” in knowledge of the MCC system may lead to...

## Key facts

- **NIH application ID:** 9942494
- **Project number:** 5R01HL136961-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Richard Charles Boucher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $646,802
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942494

## Citation

> US National Institutes of Health, RePORTER application 9942494, Multiscale Biochemical/Biophysical Integration of Pulmonary Mucus Transport (5R01HL136961-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9942494. Licensed CC0.

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