High-throughput screening for modulators of cellular contractile force

TL;DR

This study developed a high-throughput screening platform targeting cellular contractile forces to identify new drug candidates for asthma and glaucoma, demonstrating rapid screening capabilities and potential for physiological relevance.

Contribution

The paper introduces a novel force-based high-throughput screening method for discovering drugs that modulate cellular contractile forces, directly linking cellular mechanics to therapeutic discovery.

Findings

Identified several drug candidates for asthma and glaucoma.

Achieved screening rates of 1000 compounds per day.

Established a physiologically relevant force-based screening platform.

Abstract

When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signaling intermediates with poorly defined relationship to such a physiological endpoint. Using cellular force as the target, here we screened libraries to identify novel drug candidates in the case of human airway smooth muscle cells in the context of asthma, and also in the case of Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.