A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration in Pulmonary Arterial Hypertension

Authors

Tamanna Islam
Jacob Hooper
Xiaojun Zhang
Clarissa Garcia
Md Mahedi Hasan
David H Drewry
Mohammad Anwar Hossain
Taslim A Al-Hilal

Language

English

Publication Date

10-7-2025

Journal

Biomaterials Science

DOI

10.1039/d5bm00224a

PMID

40904251

PMCID

PMC12409394

PubMedCentral® Posted Date

9-4-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules. Here, for the first time, we introduce a bioengineered platform suitable for screening small molecule inhibitors targeting kinase pathways that are potentially linked to ECM-mediated directed cell migration in PAH. We used a photolithographic technique to develop mechanically patterned hydrogels with alternative stripes of soft and stiff bars representing the alternating stiffness regions of PAH ECM. Employing our bioengineered platform, we demonstrated the directional cell migration capacity of PACs and found that PAH-smooth muscle cells (SMCs) showed the highest ability to migrate from soft-stiff regions. Screening of different kinase inhibitors identified the role of JAK/STAT as a mechanosensor in the PAH-SMC-specific directional cell migration. Our study highlighted the use of a mechanically patterned bioengineering platform to identify new drug targets specific to the machinery involved in directional cell migration in PAH.

Keywords

Cell Movement, Hydrogels, Humans, Pulmonary Arterial Hypertension, Bioengineering, Myocytes, Smooth Muscle, Animals, Extracellular Matrix, Protein Kinase Inhibitors, Pulmonary Artery, Cells, Cultured

Published Open-Access

yes

Recommended Citation

Islam, Tamanna; Hooper, Jacob; Zhang, Xiaojun; et al., "A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration in Pulmonary Arterial Hypertension" (2025). Faculty, Staff and Student Publications. 5855.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5855