Dynamic regulation of single-cell contractile heterogeneity in the human trabecular meshwork

Collagen IV drives primary human trabecular meshwork cells toward a highly contractile state, while fibronectin maintains persistently heterogeneous low contractility.

• Why it matters: Glaucoma-linked changes in trabecular meshwork mechanics depend on how individual cells regulate contractility, but single-cell, time-resolved control across ECM contexts is unclear.
• What they did: Using a high-throughput single-cell contractility assay, time-resolved contraction was measured under defined ECM compositions, substrate stiffnesses, and pharmacologic perturbations, then related to intracellular protein abundance.
• The result: Dexamethasone selectively prolonged contractile activity in the most active cells, but this glucocorticoid responsiveness was constrained by increasing stiffness and absent on pathologically stiff substrates; ROCK inhibition collapsed heterogeneity into uniformly low contractility.

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