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Intermediate filaments (IFs) formed by vimentin are less understood than their cytoskeletal partners, microtubules and F‐actin, but the unique physical properties of IFs, especially their resistance to large deformations, initially suggest a mechanical function. Indeed, vimentin IFs help regulate cell mechanics and contractility, and in crowded 3D environments they protect the nucleus during cell migration. Recently, a multitude of studies, often using genetic or proteomic screenings show that vimentin has many non‐mechanical functions within and outside of cells. These include signaling roles in wound healing, lipogenesis, sterol processing, and various functions related to extracellular and cell surface vimentin. Extracellular vimentin is implicated in marking circulating tumor cells, promoting neural repair, and mediating the invasion of host cells by viruses, including SARS‐CoV, or bacteria such asListeriaandStreptococcus. These findings underscore the fundamental role of vimentin in not only cell mechanics but also a range of physiological functions. Also see the video abstract herehttps://youtu.be/YPfoddqvz-g.

Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major contributing factor to the increased pressure characteristic of primary open‐angle glaucoma. New treatments for glaucoma are being developed using actin depolymerizers and rho kinase inhibitors to address this increased stiffness. However, these agents have off‐target effects and are not as potent as had been hoped. We have developed a micellar nanocarrier assembled from poly(ethylene glycol)‐bl‐poly(propylene sulfide) copolymers capable of encapsulating latrunculin A (Lat A) with the goal of modulating SC cell stiffness. Lat A‐loaded nanocarriers were similar in size and morphology to unloaded poly (ethylene glycol)‐bl‐poly(propylene sulfide) (PEG‐bl‐PPS) micelles, loaded Lat A at 62% encapsulation efficiency, and retained loaded Lat A for at least 22 days. The continued functional activity of Lat A following encapsulation within micelles was verified in murine macrophages, which are known to display decreased endocytosis in response to Lat A‐dependent cytoskeletal disruption. Endocytic inhibition remained unchanged when comparing equal concentrations of micelle‐loaded versus free form Lat A. Uptake of Lat A‐loaded micelles by human SC cells was verifiedin vitrowith no sign of cytotoxicity, and modulation of SC cell stiffness was measured by atomic force microscopy. Lat A‐loaded micelles significantly decreased SC cell stiffness, which resulted in visible changes in cell morphology as observed by confocal microscopy. Our results demonstrate that PEG‐bl‐PPS micelles represent a tunable platform for the controlled intracellular delivery of latrunculin. These self‐assembled polymeric nanobiomaterials may support the rational design and engineering of delivery systems for the treatment of glaucoma. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1771–1779, 2018.