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Catch-slip behavior observed upon rupturing membrane-cytoskeleton bonds

Rajasekharan, V;Sreenivasan, eK;Pereira, FA;Farrell, B;

Cells are capable of cytoskeleton remodeling in response to environmental cues at the plasma membrane. The propensity to remodel in response to a mechanical stimulus is reflected in part by the lifetime of the membrane-cytoskeleton bonds upon application of a tensile loading rate. We measure the lifetime and force to rupture membrane-cytoskeleton linkages of a head and neck squamous cell carcinoma (HNSCC) cell line, HN-31 by applying a tensile loading rate (< 60 pN/s) with a handle bound to a cell, while monitoring the displacement of the handle at 2 kHz after averaging. We observe the lifetime increases with loading rate, rf to a maximum after which it decreases with further increase in rf. This biphasic relationship appears insensitive to drugs that target microtubule assembly, but is no longer detectable, i.e., lifetime is independent of rf in cells with reduced active Rho-GTPases. The loading rate-time relationship resembles catch-slip behavior reported upon applying tensile loads to separate protein complexes. Under small loads the bonds catch to increase lifetimes, under larger loads their lifetime shortens and they dissociate in a slip-like manner. Our data conforms to a model that considers the membrane-cytoskeleton bonds exhibit a load-dependent conformational change and dissociate via two pathways. We also find the membrane-cytoskeleton linkages strengthen with stationary compressive load, FSC (|FSC| < 40 pN), and conclude this metastatic cell line responds to small mechanical stimuli by promoting cytoskeleton remodeling as evident by observing F-actin within the membrane nanotube (10 m length) formed after bond rupture.