How cancer cells respond to different mechanical environments remains elusive. Here, we investigated the tension in single focal adhesions of MDA-MB-231 (metastatic breast cancer cells) and MCF-10A (normal human breast cells) cells on substrates of varying stiffness using single-cell measurements. Tension measurements in single focal adhesions using an improved FRET-based tension sensor showed that the tension in focal adhesions of MDA-MB-231 cells increased on stiffer substrates while the tension in MCF-10A cells exhibited no apparent change against the substrate stiffness. Viscoelasticity measurements using magnetic tweezers showed that the power-law exponent of MDA-MB-231 cells decreased on stiffer substrates whereas MCF-10A cells had similar exponents throughout the whole stiffness, indicating that MDA-MB-231 cells change their viscoelasticity on stiffer substrates. Such changes in tension in focal adhesions and viscoelasticity against the substrate stiffness represent an adaptability of cancer cells in mechanical environments, which can facilitate the metastasis of cancer cells to different tissues.
During the biosynthesis of tail-anchored (TA) membrane proteins, their single C-terminal trans-membrane segment is inserted into the endoplasmic reticulum (ER) membrane for orientating the functional domain(s) towards the cytosolic side of the cell. Recent work has uncovered the "Get pathway (guided entry of Tail-anchored protein)", which is responsible for ER targeting of tail-anchored proteins. The Get system consists of Get1, Get2, Get3, Get4 and Get5 proteins. Although structural information and the individual roles of most components of this system have been defined, the interactions and interplay between them remain to be elucidated. Here, we investigated the interactions between Get3 and the Get4/Get5 complex (Get4/5) from Saccharomyces cerevisiae [1]. We show that Get3 interacts with Get4/5 via an interface dominated by electrostatic forces. Using isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS), we further demonstrate that the Get3 homodimer interacts with two copies of the Get4/5 complex to form an extended conformation in solution.
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