Particulate Matter Composition Drives Differential Molecular and Morphological Responses in Lung Epithelial Cells

Overview

Journal PNAS Nexus

Specialty General Medicine

Date 2023 Dec 29

PMID 38156290

Authors

Sean M Engels

Pratik Kamat

G Stavros Pafilis

Yukang Li

Anshika Agrawal

Daniel J Haller

Jude M Phillip

Lydia M Contreras

Affiliations

Soon will be listed here.

Abstract

Particulate matter (PM) is a ubiquitous component of air pollution that is epidemiologically linked to human pulmonary diseases. PM chemical composition varies widely, and the development of high-throughput experimental techniques enables direct profiling of cellular effects using compositionally unique PM mixtures. Here, we show that in a human bronchial epithelial cell model, exposure to three chemically distinct PM mixtures drive unique cell viability patterns, transcriptional remodeling, and the emergence of distinct morphological subtypes. Specifically, PM mixtures modulate cell viability, DNA damage responses, and induce the remodeling of gene expression associated with cell morphology, extracellular matrix organization, and cellular motility. Profiling cellular responses showed that cell morphologies change in a PM composition-dependent manner. Finally, we observed that PM mixtures with higher cadmium content induced increased DNA damage and drove redistribution among morphological subtypes. Our results demonstrate that quantitative measurement of individual cellular morphologies provides a robust, high-throughput approach to gauge the effects of environmental stressors on biological systems and score cellular susceptibilities to pollution.

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