In this Letter, we present a new mechanism under the action of which a shear thickening suspension transitions from a continuous to a discontinuous regime. This transition occurs by adding high ...concentrations of large spheres to a continuous shear thickening suspension. We show that the solid volume fraction of the interstitial shear thickening matrix is locally enhanced due to the presence of large particles and the excluded-volume shells surrounding the large particles, thus leading to a continuous to discontinuous shear thickening transition at the local scale.
Abstract The transmembrane death receptor Fas transduces apoptotic signals upon binding its ligand, FasL. Although Fas is highly expressed in cancer cells, insufficient cell surface Fas expression ...desensitizes cancer cells to Fas-induced apoptosis. Here, we show that the increase in Fas microaggregate formation on the plasma membrane in response to the inhibition of endocytosis sensitizes cancer cells to Fas-induced apoptosis. We used a clinically accessible Rho-kinase inhibitor, fasudil, that reduces endocytosis dynamics by increasing plasma membrane tension. In combination with exogenous soluble FasL (sFasL), fasudil promoted cancer cell apoptosis, but this collaborative effect was substantially weaker in nonmalignant cells. The combination of sFasL and fasudil prevented glioblastoma cell growth in embryonic stem cell-derived brain organoids and induced tumor regression in a xenograft mouse model. Our results demonstrate that sFasL has strong potential for apoptosis-directed cancer therapy when Fas microaggregate formation is augmented by mechano-inhibition of endocytosis.
Deformability of the plasma membrane, the outermost surface of metazoan cells, allows cells to be dynamic, mobile and flexible. Factors that affect this deformability, such as tension on the ...membrane, can regulate a myriad of cellular functions, including membrane resealing, cell motility, polarisation, shape maintenance, membrane area control and endocytic vesicle trafficking. This review focuses on mechanoregulation of clathrin‐mediated endocytosis (CME). We first delineate the origins of cell membrane tension and the factors that yield to its spatial and temporal fluctuations within cells. We then review the recent literature demonstrating that tension on the membrane is a fast‐acting and reversible regulator of CME. Finally, we discuss tension‐based regulation of endocytic clathrin coat formation during physiological processes.
Review: Intracellular membrane trafficking pathways have a reciprocal relationship with plasma membrane mechanics. This review discusses insights gained from recent literature which demonstrates that membrane tension works as a fast‐acting and reversible regulator of clathrin‐mediated endocytosis in a wide range of physiological processes.
A cornstarch suspension is the quintessential particulate system that exhibits shear thickening. By adding large non-Brownian spheres to a cornstarch suspension, we show that shear thickening can be ...significantly enhanced. More precisely, the shear-thickening transition is found to be increasingly shifted to lower critical shear rates. This influence of the large particles on the discontinuous shear-thickening transition is shown to be more dramatic than that on the viscosity or the yield stress of the suspension.
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