The Mechanical Response of Cells,
Cross-Link Dynamics and Mechano-Sensing

Professor John Crocker
University of Pennsylvania

Date: Thursday, January 19, 2006
Time: 4:00 p.m.
Place: Engineering II, Room 3361

ABSTRACT

While cells’ responses to mechanical stimuli are seen as increasingly important for understanding cell biology, how to best measure, interpret and model cells mechanical properties remains unclear.  We determine the frequency-dependent shear modulus of cultured mammalian cells using four different methods, both novel and well established.  This approach clarifies the effects of ATP-dependent processes, cell regional variations and cytoskeletal heterogeneity on the interpretation of such measurements. Our results clearly indicate two qualitatively similar but distinct mechanical responses, corresponding to the cortical and intracellular networks, each having an unusual, weak power-law form at low frequency.  Comparison with recent reconstituted biopolymer models suggests such a response is determined by the dynamics of network cross-linking proteins.

We propose a simple cytoskeletal architecture based on the force-induced serial unfolding of domains in protein cross-links such as filamin. In simulation, that slow deformation of a simplified model network leads to a distribution of internal stresses that can in turn reproduce cells’ unusual frequency-dependent stiffness. Moreover, in simulated networks the degree of domain unfolding corresponds closely to network deformation, suggesting that by modulating the binding of signaling species, cross-link domain unfolding could enable the biochemical transduction of cytoskeletal deformation at the cellular scale.