Catch-slip behavior observed upon rupturing membrane-cytoskeleton bonds

Abstract

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, to a maximum after which it decreases with further increase in . This biphasic relationship appears insensitive to drugs that target microtubule assembly, but is no longer detectable, i.e., lifetime is independent of 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, (| | < 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 µm length) formed after bond rupture.